绵羊IGFBP家族基因克隆和IGF系统基因的时空表达谱及IGF-Ⅰ与体重性状的相关分析研究
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摘要
IGFs介导生长激素(GH)促进动物生长的功能,在动物的胚胎及生后的生长发育过程中具有重要的作用,调节糖类代谢、脂肪代谢、蛋白合成、肝脏功能、线性生长等。IGFBPs在体内循环系统中与IGFs结合,调控IGFs的半衰期,提高IGFs的生理活性。肝脏和局部组织分泌的IGFs共同调控各个组织的生长与发育,从而促进动物机体的生长。
本研究应用RT-PCR和克隆技术从绵羊肝脏组织总RNA中克隆出绵羊IGFBPs家族中的IGFBP-1、IGFBP-3、IGFBP-4、IGFBP-5、IGFBP-6和IGFBP-7等6个基因的mRNA序列。序列分析表明6个基因的开放阅读框(ORE)全长分别为792bp、882bp、777bp、816bp、711bp和849bp,分别编码263、293、258、271、236和282个氨基酸;6个基因的碱基组成中G+C含量在60.23～68.34%之间,高于A+T;家族基因间的CDS序列的同源性在0.334～0.548之间,氨基酸同源性在0.124～0.426之间。进化分析表明IGFBPs家族基因分为1GFBP-1、IGFBP-3、IGFBP-6和1GFBP-7等4个进化支,在IGFBP-1进化支分化出IGFBP-2和IGFBP-4基因,在1GFBP-3进化支分化出IGFBP-5基因,而IGFBP-6和IGFBP-7进化支未分化出基因;结构及功能预测表明6个基因的氨基酸序列具有N-端和C-端保守区域以及中央的高变区域,在N-端分享了5-6个域内二硫键,在C-端分享了3个域内二硫键(IGFBP-7仅1个二硫键);在N-端的前30AA内都含有一个信号肽区域,整个序列中具有明显的疏水性区域(IGFBP-7亲水性区域较多),在IGFBP-1和IGFBP-7中分别具有1个和2个跨膜区,翻译后修饰主要为磷酸化和糖基化,二级结构以无规卷曲为主,其次为α-螺旋,β-折叠最少,6个基因的N-端具有一个IGFBP_ N功能域,而在C-端存在一个甲状腺球蛋白-1域(IGFBP-7为Ig-like域)。同时,还具有较多的豆蔻酰化位点、酪蛋白激酶Ⅱ磷酸化位点和蛋白激酶C磷酸化位点等。
采用QRT-PCR技术研究了绵羊IGF系统基因在生长期的时空表达,结果表明:在各个时间点的各个组织中都检测到IGF系统基因的表达,但相对表达量存在一定的差异,IGF-Ⅰ和IGF-Ⅱ主要产生于肝脏组织,肝脏组织的表达高于大脑、心脏、皮肤和肌肉等组织,IGF-ⅠR、IGF-ⅡR和IGFBPs跟生后绵羊机体局部组织的具体功能而表现出较大的差异。IGF系统的大部分基因在各个时间点的表达呈现相似的表达规律,在大脑组织,11个基因在6个时间点的表达规律一致,呈波浪型变化,在15d、105d、195d时各个基因的表达相对较高,可能是应答于外界的营养条件而表现出较高的峰值,在60d、150d、240d时的表达相对较低,IGF-ⅠR在240d时表达较高,在195d→240d时IGF-ⅠR起了主要的作用;在皮肤组织,IGF-Ⅰ、IGF-Ⅱ、IGF-2R、IGFBP-1、1GFBP-4、IGFBP-6和IGFBP-7基因的表达规律一致,在15d和60d时的表达相对较高,IGFBP-1和IGFBP-3基因在整个过程中逐渐降低,对皮肤的作用较弱,IGF-ⅠR基因在105d时的表达最低,而后其作用逐渐增强,IGFBP-5基因在60d时的表达相对较高,其他几个时间点上的表达保持稳定;在肌肉组织,IGF-Ⅰ、IGF-Ⅱ、IGF-ⅠR、IGF-2R、IGFBP-2和IGFBP-6基因的表达规律一致,在150d时的表达相对较高,IGFBP-1和IGFBP-7基因与前6个基因的表达相反,在肌肉中的作用是抑制了肌细胞的增殖与分化,IGFBP-3、IGFBP-4和IGFBP-5基因的表达较平衡,在肌肉中的作用较稳定;在肝脏组织,各个基因的表达规律倾向一致,在105d时除IGFBP-2和IGFBP-4基因在150d时的表达相对较高外其他基因在105d时的表达相对较高,在195d后,两个受体基因的表达比较稳定;在心脏组织中,除IGF-ⅠR基因外,其他10个基因的表达规律一致,在105d时的表达相对较高,150d后各个基因的表达倾向稳定。11个基因在肝脏和大脑等组织的表达表现为不同程度的正相关,心脏组织中IGF-ⅠR的表达除与IGF-ⅡR、IGFBP-1基因呈正相关外,与其他9个基因呈不同程度的负相关,其他基因则与皮肤组织、肝脏和大脑组织的表达相关性一致,肌肉中IGFBP-1基因与1GFBP-3、IGFBP-4和IGFBP-5基因间呈不同程度负相关,IGF-Ⅰ基因与IGFBP-7基因间呈显著的负相关,与其他基因或其他基因间呈不同程度正相关;皮肤组织中IGF-Ⅰ和IGF-Ⅱ基因与其他基因的相关性趋向一致,IGF-ⅠR与其他所有基因都呈负相关,7种蛋白基因之间呈不同程度的正负相关。
采用SSCP技术研究IGF-Ⅰ基因的外显子前导区和外显子3的SNP位点,结果表明:P-1和P-2引物扩增的序列中是C→G和A→G突变,以A、C和AA、CC为优势等位基因与优势等位基因型;P-1的PIC含量在群体和各个家系中分别为0.276、0.252～0.303,为中度多态性,P-2分别为0.237、0.171～0.279,为中低度多态性;P-1的SNP位点与凉山半细毛羊的初生体重呈在显著的相关,P-2的SNP位点与断奶体重和断奶日增重存在极显著相关:单倍型以H2和H3占主导地位,组合型的H1H1、H1H3和H2H2的初生体重极显著高于其他几种组合型,H2H2组合型的断奶体重和断奶日增重极显著高于其他几种组合型,这两个SNP位点可用于凉山半细毛羊的早期生长性状的SNP辅助选择育种。
Insulin like growth factorⅠand Insulin like growth factorⅡstimulate the growth of animal in embryo period and the developing of post birth period with mediating the neuroendocrine function of chondrotropic hormone.It is vital physiological effectiveness which are regulating carbohydrate metabolism,fat metabolism,protein synthesis,liver function and linear growth of all livestock.IGFs bind mainly IGFBP-1,IGFBP-2,IGFBP-3,IGFBP-4,IGFBP-5,IGFBP-6 and IGFBP-7 in circulation system of the animal organisms with the stimulating growth function throughout secreting from animal liver and carrying to the ambitus tissues.we have researched the IGF system genes regulating the growth of liangshan semi-wool sheep with Real time PCR、SSCP and cloning technique.
Here we cloned mRNA of IGFBP family genes from total RNA of liver in liangshan semi-wool sheep by RT-PCR with exception for IGFBP-2.Sequence analysis indicated that the ovine IGFBP-1, IGFBP-3,IGFBP-4,IGFBP-5,IGFBP-6 and IGFBP-7 cDNA cloned were 792bp,882bp,777bp, 816bp,711bp and 849bp in length(GenBank accession number FJ589640,FJ752574,EU882037, EU727460,EU862545 and FJ589640) and the open reading frame encode a deduced protein with 263,293,258,271,236 and 282 amino acids residues respectively.The comparison of the duduced amino acids sequence of IGFBPs(including IGFBP-2) showed that the eds sequence homology were 0.334～0.548,and the animo acids homology were 0.124～0.426.Phylogenetic analysis indicates that the IGFBPs segregated into four distinct clades:IGFBP-1,IGFBP-3,IGFBP-6 and IGFBP-7.Subsequent gene duplication events within the IGFBP-1 and IGFBP-3 clades resulted in the production and divergence of IGFBP-2 and IGFBP-4 within the IGFBP-1 clade and IGFBP-5 in the IGFBP-3 clade.The primary structures of ovine IGFBPs appear to contain three distinct domains:the conserved N-terminal domain,the highly variable midregion,and the conserved C-terminal domain.the N-terminal domain of IGFBP-1,IGFBP-3,IGFBP-4,IGFBP-5,IGFBP-7 formed the six disulfide bridges(five in the case of IGFBP-6) with neighboring Cys within the conserved 12 Cys and the C-terminal domain contained the three disulfide bridges(only one of IGFBP-7) with the same modus of the N-terminal domain.there is a signal peptide within the fore 30 animo acid of N-terminal which possess a IGFBP_N functional domain and a Thyroglobulin type-1 domain(Ig-like of IGFBP-7) of the C-terminal of cloned six genes which exist large Casein kinaseⅡphosphorylation sites,Protein kinase C phosphorylation sites,Tyrosine kinase phosphorylation site,N-glycosylation sites and O-glycosylation sites.
We researched the expression of IGF system genes in different tisssues with different growth period by QRT-PCR technique.The analysis indicated that all tissues we gained from liangshan semi-wool sheep were tested the expression of IGF system genes in different growth period and were different of relative expression with the different function of.the ambitus tissues.In brain tissue,there were similar to the expression mode of the eleven genes of IGF system with wave change,and were relatively high expression level at 15~(th),105~(th) and 195~(th) day against the 60~(th),150~(th) and 240~(th) day.In skin tissue,IGF-Ⅰ,IGF-Ⅱ,IGF-2R,IGFBP-1,IGFBP-4,IGFBP-6 and IGFBP-7 were similar to the expression mode with relatively high level at 15~(th) and 60~(th) day.However,the expression mode of IGFBP-1 and -3 were gradually lower from 15~(th) to 240~(th) day and only high expression of IGFBP-5 at 60~(th) day.In muslc tissue,there were similar to the expression mode of IGF-Ⅰ,IGF-Ⅱ, IGF-ⅠR,IGF-ⅡR,IGFBP-2 and IGFBP-6 and high expressional level at 150~(th) day,against IGFBP-1 with the function of inhibiting myocyte proliferation and differentiation,and stabilizational expression of IGFBP-4 and IGFBP-5.In liver tissue,there were similar to the expression mode of all IGF system genes during the different period with exception for IGFBP-2 at 105~(th) day and IGFBP-4 at 150~(th) day.In heart tissue,thoughout IGF system genes were similar to the expression mode with exception for IGF-ⅠR and high expressional level at 105~(th) day and tropesis stabilizational expression from 150~(th) to 240~(th) day.There were the positive correlation to different degree of the IGF system genes in skin,liver and brain tissues,and the same correlation with exception for negative correlation to different degree between IGF-ⅠR with IGF-Ⅰ,IGF-Ⅱ,IGF-ⅡR,IGFBP-2,IGFBP-3,IGFBP-4,IGFBP-5,IGFBP-6 and IGFBP-7 in heart tissue.In musle tissue,there were the positive correlation to different degree of the IGF system genes with exception for negative correlation to different degree between IGFBP-1 and IGFBP-3,IGFBP-4 and IGFBP-5,IGF-Ⅰand GFBP-7.It means that the expression were differentiated in tissues with the different function of the ambitus tissues.
There were the two SNP site which have detected within exon 3 and exon leader region respectively with the p-1 and p-2 primers of the designed with complete exons of IGF-Ⅰin 587 individuals of liangshan semi-wool sheep by PCR-SSCP.The two SNP site were C→G and A→G mutation which the allele A and C were the predominant allele with the p-1 and p-2 primers.Polymorphism Information Content of the p-1 primer were 0.276 and 0.252～0.303,and the p-2 primer were 0.237 and 0.171～0.279 in the population and the 8 six half-sib family population respectively.The variance and relationship analysis showed that the SNP of the p-1 primer influenced significantly birth weight trait(p＜0.05) and the SNP of the p-2 primer influenced high significantly on Weaning weight and the Weaning daily weight traits and no significantly 18 months weight and 30 months weight traits.The haplotype H2 and H3 were the predominant haplotype and the combined H2H2,H1H2 and H1H3 influence significantly birth weight,18 months weight and 30 months weight traits.It may be apply to assisted selective breeding with the two SNPs in liangshan semi-wool sheep.
本研究应用RT-PCR和克隆技术从绵羊肝脏组织总RNA中克隆出绵羊IGFBPs家族中的IGFBP-1、IGFBP-3、IGFBP-4、IGFBP-5、IGFBP-6和IGFBP-7等6个基因的mRNA序列。序列分析表明6个基因的开放阅读框(ORE)全长分别为792bp、882bp、777bp、816bp、711bp和849bp,分别编码263、293、258、271、236和282个氨基酸;6个基因的碱基组成中G+C含量在60.23～68.34%之间,高于A+T;家族基因间的CDS序列的同源性在0.334～0.548之间,氨基酸同源性在0.124～0.426之间。进化分析表明IGFBPs家族基因分为1GFBP-1、IGFBP-3、IGFBP-6和1GFBP-7等4个进化支,在IGFBP-1进化支分化出IGFBP-2和IGFBP-4基因,在1GFBP-3进化支分化出IGFBP-5基因,而IGFBP-6和IGFBP-7进化支未分化出基因;结构及功能预测表明6个基因的氨基酸序列具有N-端和C-端保守区域以及中央的高变区域,在N-端分享了5-6个域内二硫键,在C-端分享了3个域内二硫键(IGFBP-7仅1个二硫键);在N-端的前30AA内都含有一个信号肽区域,整个序列中具有明显的疏水性区域(IGFBP-7亲水性区域较多),在IGFBP-1和IGFBP-7中分别具有1个和2个跨膜区,翻译后修饰主要为磷酸化和糖基化,二级结构以无规卷曲为主,其次为α-螺旋,β-折叠最少,6个基因的N-端具有一个IGFBP_ N功能域,而在C-端存在一个甲状腺球蛋白-1域(IGFBP-7为Ig-like域)。同时,还具有较多的豆蔻酰化位点、酪蛋白激酶Ⅱ磷酸化位点和蛋白激酶C磷酸化位点等。
采用QRT-PCR技术研究了绵羊IGF系统基因在生长期的时空表达,结果表明:在各个时间点的各个组织中都检测到IGF系统基因的表达,但相对表达量存在一定的差异,IGF-Ⅰ和IGF-Ⅱ主要产生于肝脏组织,肝脏组织的表达高于大脑、心脏、皮肤和肌肉等组织,IGF-ⅠR、IGF-ⅡR和IGFBPs跟生后绵羊机体局部组织的具体功能而表现出较大的差异。IGF系统的大部分基因在各个时间点的表达呈现相似的表达规律,在大脑组织,11个基因在6个时间点的表达规律一致,呈波浪型变化,在15d、105d、195d时各个基因的表达相对较高,可能是应答于外界的营养条件而表现出较高的峰值,在60d、150d、240d时的表达相对较低,IGF-ⅠR在240d时表达较高,在195d→240d时IGF-ⅠR起了主要的作用;在皮肤组织,IGF-Ⅰ、IGF-Ⅱ、IGF-2R、IGFBP-1、1GFBP-4、IGFBP-6和IGFBP-7基因的表达规律一致,在15d和60d时的表达相对较高,IGFBP-1和IGFBP-3基因在整个过程中逐渐降低,对皮肤的作用较弱,IGF-ⅠR基因在105d时的表达最低,而后其作用逐渐增强,IGFBP-5基因在60d时的表达相对较高,其他几个时间点上的表达保持稳定;在肌肉组织,IGF-Ⅰ、IGF-Ⅱ、IGF-ⅠR、IGF-2R、IGFBP-2和IGFBP-6基因的表达规律一致,在150d时的表达相对较高,IGFBP-1和IGFBP-7基因与前6个基因的表达相反,在肌肉中的作用是抑制了肌细胞的增殖与分化,IGFBP-3、IGFBP-4和IGFBP-5基因的表达较平衡,在肌肉中的作用较稳定;在肝脏组织,各个基因的表达规律倾向一致,在105d时除IGFBP-2和IGFBP-4基因在150d时的表达相对较高外其他基因在105d时的表达相对较高,在195d后,两个受体基因的表达比较稳定;在心脏组织中,除IGF-ⅠR基因外,其他10个基因的表达规律一致,在105d时的表达相对较高,150d后各个基因的表达倾向稳定。11个基因在肝脏和大脑等组织的表达表现为不同程度的正相关,心脏组织中IGF-ⅠR的表达除与IGF-ⅡR、IGFBP-1基因呈正相关外,与其他9个基因呈不同程度的负相关,其他基因则与皮肤组织、肝脏和大脑组织的表达相关性一致,肌肉中IGFBP-1基因与1GFBP-3、IGFBP-4和IGFBP-5基因间呈不同程度负相关,IGF-Ⅰ基因与IGFBP-7基因间呈显著的负相关,与其他基因或其他基因间呈不同程度正相关;皮肤组织中IGF-Ⅰ和IGF-Ⅱ基因与其他基因的相关性趋向一致,IGF-ⅠR与其他所有基因都呈负相关,7种蛋白基因之间呈不同程度的正负相关。
采用SSCP技术研究IGF-Ⅰ基因的外显子前导区和外显子3的SNP位点,结果表明:P-1和P-2引物扩增的序列中是C→G和A→G突变,以A、C和AA、CC为优势等位基因与优势等位基因型;P-1的PIC含量在群体和各个家系中分别为0.276、0.252～0.303,为中度多态性,P-2分别为0.237、0.171～0.279,为中低度多态性;P-1的SNP位点与凉山半细毛羊的初生体重呈在显著的相关,P-2的SNP位点与断奶体重和断奶日增重存在极显著相关:单倍型以H2和H3占主导地位,组合型的H1H1、H1H3和H2H2的初生体重极显著高于其他几种组合型,H2H2组合型的断奶体重和断奶日增重极显著高于其他几种组合型,这两个SNP位点可用于凉山半细毛羊的早期生长性状的SNP辅助选择育种。
Insulin like growth factorⅠand Insulin like growth factorⅡstimulate the growth of animal in embryo period and the developing of post birth period with mediating the neuroendocrine function of chondrotropic hormone.It is vital physiological effectiveness which are regulating carbohydrate metabolism,fat metabolism,protein synthesis,liver function and linear growth of all livestock.IGFs bind mainly IGFBP-1,IGFBP-2,IGFBP-3,IGFBP-4,IGFBP-5,IGFBP-6 and IGFBP-7 in circulation system of the animal organisms with the stimulating growth function throughout secreting from animal liver and carrying to the ambitus tissues.we have researched the IGF system genes regulating the growth of liangshan semi-wool sheep with Real time PCR、SSCP and cloning technique.
Here we cloned mRNA of IGFBP family genes from total RNA of liver in liangshan semi-wool sheep by RT-PCR with exception for IGFBP-2.Sequence analysis indicated that the ovine IGFBP-1, IGFBP-3,IGFBP-4,IGFBP-5,IGFBP-6 and IGFBP-7 cDNA cloned were 792bp,882bp,777bp, 816bp,711bp and 849bp in length(GenBank accession number FJ589640,FJ752574,EU882037, EU727460,EU862545 and FJ589640) and the open reading frame encode a deduced protein with 263,293,258,271,236 and 282 amino acids residues respectively.The comparison of the duduced amino acids sequence of IGFBPs(including IGFBP-2) showed that the eds sequence homology were 0.334～0.548,and the animo acids homology were 0.124～0.426.Phylogenetic analysis indicates that the IGFBPs segregated into four distinct clades:IGFBP-1,IGFBP-3,IGFBP-6 and IGFBP-7.Subsequent gene duplication events within the IGFBP-1 and IGFBP-3 clades resulted in the production and divergence of IGFBP-2 and IGFBP-4 within the IGFBP-1 clade and IGFBP-5 in the IGFBP-3 clade.The primary structures of ovine IGFBPs appear to contain three distinct domains:the conserved N-terminal domain,the highly variable midregion,and the conserved C-terminal domain.the N-terminal domain of IGFBP-1,IGFBP-3,IGFBP-4,IGFBP-5,IGFBP-7 formed the six disulfide bridges(five in the case of IGFBP-6) with neighboring Cys within the conserved 12 Cys and the C-terminal domain contained the three disulfide bridges(only one of IGFBP-7) with the same modus of the N-terminal domain.there is a signal peptide within the fore 30 animo acid of N-terminal which possess a IGFBP_N functional domain and a Thyroglobulin type-1 domain(Ig-like of IGFBP-7) of the C-terminal of cloned six genes which exist large Casein kinaseⅡphosphorylation sites,Protein kinase C phosphorylation sites,Tyrosine kinase phosphorylation site,N-glycosylation sites and O-glycosylation sites.
We researched the expression of IGF system genes in different tisssues with different growth period by QRT-PCR technique.The analysis indicated that all tissues we gained from liangshan semi-wool sheep were tested the expression of IGF system genes in different growth period and were different of relative expression with the different function of.the ambitus tissues.In brain tissue,there were similar to the expression mode of the eleven genes of IGF system with wave change,and were relatively high expression level at 15~(th),105~(th) and 195~(th) day against the 60~(th),150~(th) and 240~(th) day.In skin tissue,IGF-Ⅰ,IGF-Ⅱ,IGF-2R,IGFBP-1,IGFBP-4,IGFBP-6 and IGFBP-7 were similar to the expression mode with relatively high level at 15~(th) and 60~(th) day.However,the expression mode of IGFBP-1 and -3 were gradually lower from 15~(th) to 240~(th) day and only high expression of IGFBP-5 at 60~(th) day.In muslc tissue,there were similar to the expression mode of IGF-Ⅰ,IGF-Ⅱ, IGF-ⅠR,IGF-ⅡR,IGFBP-2 and IGFBP-6 and high expressional level at 150~(th) day,against IGFBP-1 with the function of inhibiting myocyte proliferation and differentiation,and stabilizational expression of IGFBP-4 and IGFBP-5.In liver tissue,there were similar to the expression mode of all IGF system genes during the different period with exception for IGFBP-2 at 105~(th) day and IGFBP-4 at 150~(th) day.In heart tissue,thoughout IGF system genes were similar to the expression mode with exception for IGF-ⅠR and high expressional level at 105~(th) day and tropesis stabilizational expression from 150~(th) to 240~(th) day.There were the positive correlation to different degree of the IGF system genes in skin,liver and brain tissues,and the same correlation with exception for negative correlation to different degree between IGF-ⅠR with IGF-Ⅰ,IGF-Ⅱ,IGF-ⅡR,IGFBP-2,IGFBP-3,IGFBP-4,IGFBP-5,IGFBP-6 and IGFBP-7 in heart tissue.In musle tissue,there were the positive correlation to different degree of the IGF system genes with exception for negative correlation to different degree between IGFBP-1 and IGFBP-3,IGFBP-4 and IGFBP-5,IGF-Ⅰand GFBP-7.It means that the expression were differentiated in tissues with the different function of the ambitus tissues.
There were the two SNP site which have detected within exon 3 and exon leader region respectively with the p-1 and p-2 primers of the designed with complete exons of IGF-Ⅰin 587 individuals of liangshan semi-wool sheep by PCR-SSCP.The two SNP site were C→G and A→G mutation which the allele A and C were the predominant allele with the p-1 and p-2 primers.Polymorphism Information Content of the p-1 primer were 0.276 and 0.252～0.303,and the p-2 primer were 0.237 and 0.171～0.279 in the population and the 8 six half-sib family population respectively.The variance and relationship analysis showed that the SNP of the p-1 primer influenced significantly birth weight trait(p＜0.05) and the SNP of the p-2 primer influenced high significantly on Weaning weight and the Weaning daily weight traits and no significantly 18 months weight and 30 months weight traits.The haplotype H2 and H3 were the predominant haplotype and the combined H2H2,H1H2 and H1H3 influence significantly birth weight,18 months weight and 30 months weight traits.It may be apply to assisted selective breeding with the two SNPs in liangshan semi-wool sheep.
引文
[1]薄吾成.试论藏羊渊源[J].西北农业大学学报.1986.14(2):79-82.
[2]吴登俊.培育凉山半细毛羊的启示[J].四川草原.2003.4:5-9.
[3]陈圣偶.凉山半细毛羊的选育及其生产性能.草食家畜[J].2002.115(2):19-22.
[4]陈圣偶.李利,张红平等.凉山半细毛羊育成期生长发育的研究[J].四川草原.2002.2:57-60.
[5]李利,陈圣偶.凉山半细毛羊血液生化指标与生产性能的相关性研究[J].四川农业大学学报.2001.19(1):91-93.
[6]姜勋平,陈圣偶,刘相模.凉山半细毛羊遗传结构研究[J].四川农业大学学报.1996.14(3):457-460.
[7]李小晴,吴登俊,陈圣偶.凉山半细毛羊、山谷型藏绵羊Ag-NoRs带的比较研究.四川大学学报(自然科学版)[J].2000.37(增刊):144-147.
[8]李小晴,吴登俊,陈圣偶等.凉山半细毛羊与山谷型藏绵羊染色体核型的比较[J].西北农林科技大学学报(自然科学版).2006.34(12):11-15.[
9]李小晴,吴登俊,陈圣偶等,凉山半细毛羊、山谷型藏绵羊染色体畸变研究[J].畜牧兽医学报.2007.38(4):400-406.
[10]赵俊丽.利用微卫星标记进行凉山半细毛羊羊毛性状的QTL定位研究[M].硕士论文.四川雅安.四川农业大学.2002.
[11]贾兰平.利用微卫星标记进行凉山半细毛羊体重QTL研究[M].硕士论文.四川雅安.四川农业大学.2002.
[12]陈艺.凉山半细毛羊2号染色体遗传连锁框架图的构建及体重性状QTL定位的研究[M]..硕士论文.四川雅安.四川农业大学.2004.
[13]张明娅,吴登俊.凉山半细毛羊1号染色体微卫星遗传连锁图谱的构建[J].遗传.2005.27(4):575-578.
[14]张明娅.凉山半细毛羊1号染色体遗传连锁图和羊毛性状QTL定位研究[M].硕士论文.四川雅安.四川农业大学.2004.
[15]张鹦俊.凉山半细毛羊2号染色体羊毛性状的QTL定位研究[M].硕士论文.四川雅安.四川农业大学.2004.
[16]李辉.凉山半细毛羊QTL定位初步研究[M].博士论文.四川雅安.四川农业大学.2006.
[17]周明亮,吴登俊.绵羊3号染色体的遗传连锁图谱构建及QTL定位[J].遗传.2007.29(12):1475-1482.
[18]高爱保,吴登俊.利用微卫星标记进行凉山半细毛羊亲权鉴定的研究[J].遗传.2005.27(1):85-90.
[19]王高富,吴登俊.凉山半细毛羊微卫星标记与羊毛性状的相关分析[J].遗传.2006.28(12):1505-1512.
[20]张翔宇.凉山半细毛羊微卫星多态性与体重性状的相关分析[M].硕士论文.四川雅安.四川农业大学.2006.
[21]余敏.凉山半细毛羊资源参考群信息数据库的初步构建[M].硕士论文.四川雅安.四川农业大.2007.
[22]姜勋平,陈圣偶.凉山半细毛羊横交群重要经济性状遗传率及其相关分析[J].四川畜牧兽医 1996,1:9-10.
[23]杨平贵,吴登俊.凉山半细毛羊几个早期性状遗传参数的估测[J].畜禽业.2006.192:12-13.
[24]刘阳。凉山半细毛羊主要生产性状的遗传参数评估[M].硕士论文.四川雅安.四川农业大学.2007.
[25]Salmon W D,Daughaday W H,A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro[J].J Lab Clin Med.1957.49:825-826.
[26]Derek Le Roith C.B.,Shoshana Yakar,Jun-li Liu,et al.The Somatomedin Hypothesis:2001[J].Endocrine Reviews.2001.22(1):53-74.
[27]Murphy W R,Daughaday W H,Hartnett C.The effect of hypophysectomy and growth hormone on the incorporation of labeled sulfate into tibila epiphyseal and nasal cartilage of the rat[J].J Lab Clin Med.1956.47:715-722.
[28]Denko CW,Bergenstal DM.The effect of hypophysectomy and growth hormone on cartilage sulfate metabolism[J].Proc Soc Exp Biol Med.1955.84:603-605.
[29]Daughaday W H,Reeder C.Synchronous activation of DNA synthesis in hypophysectomized rat cartilage by growth hormone[J].J Lab Clin Med 1966.68:357-368.
[30]Garland J T LME,Kozak S,Daughaday W H:Stimulation of DNA synthesis in isolated chondrocytes by sulfation factor[J].Endocrinology.1972.90:1086-1090.
[31]Daughaday WH,Hall K,Raben MS,et al.Somatomedin:proposed designation for sulphation factor[J].Nature.1972.235:107.
[32]Klapper D G,Svoboda M E,Van Wyk J J.Sequence analysis of somatomedin-C:confirmation of identity with insulin-like growth factor I[J].Endocrinology.1983.112:2215-2217.
[33]Rinderknecht E,Humbel RE.The amino acid sequence of human insulin-like growth factor Ⅰ and its structural homology with proinsulin[J].J Biol Chem.1978.253:2769-2776.
[34]Randle P J.Plasma-insulin activity in hypopituitarism[J].Lancet 1954.1:809-810.
[35]Blundell T L,Bedarkar S,Rinderknecht E.Insulin-like growth factor:a model for tertiary structure accounting for immunoreactivity and receptor binding[J].Proc Natl Acad Sci.1978.75:180-184.
[36]Blundell TL,Bedarkar S,Humbel RE.Tertiary structures,receptor binding,and antigenicity of insulin-like growth factors[J].Fed Proc.1983.42:2592-2597.
[37]Berelowitz M,Szabo M,Frohman LA.et al.Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary[J].Science.1981.212:1279-1281.
[38]D'Ercole AJ,Applewhite GT,Underwood LE.et al.Evidence that somatomedin is synthesized by multiple tissues in the fetus[J].Dev Biol.1980.75:315-328.
[39]Jansen M,van Schaik FM,Ricker AT.et al.Sequence of cDNAencoding human insulin-like growth factor Ⅰ precursor[J].Nature.1983.306:609-611.
[40]Kajimoto Y,Rotwein P.Structure and expression of a chicken insulin-like growth factor Ⅰprecursor[J].Mol Endocrinol.1989.3:1907-1913.
[41]Lowe Jr WL,Lasky SR,LeRoith D.Distribution and regulation of rat insulin-like growth factor Ⅰmessenger ribonucleic acids encoding alternative carboxy-terminal E-peptides:evidence for differential processing and regulation in liver[J].Mol Endocrinol.1988.2:528-535.
[42]Lowe WL,Roberts Jr CT,Lasky SR.Differential expression of alternative 59 untranslated regions in mRNAs encoding rat insulin-like growth factor I[J].Proc Natl Acad Sci USA.1987.84:8946-8950.
[43]Isaksson OG,Jansson JO,Gause IA.Growth hormone stimulates longitudinal bone growth directly[J].Science.1982.216:1237-1239.
[44] Schlechter NL, Russell SM, Spencer EM. et al. Evidence suggesting that the direct growth-promoting effect of growth hormone on cartilage in vivo is mediated by local production of somatomedin[J]. Proc Natl Acad Sci USA. 1986. 83:7932-7934.
[45] Nilsson A, Isgaard J, Lindahl A. et al. Regulation by growth hormone of number of chondrocytes containing IGF-I in rat growth plate[J]. Science. 1986.233:571-574.
[46] Green H, Morikawa M, Nixon T. et al. A dual effector theory of growth-hormone action[J]. Differentiation. 1985.29:195-198.
[47] Hiragun A, Sato M, Mitsui H. et al. Establishment of a clonal cell line that differentiates into adipose cells in vitro[J]. In Vitro 1980,16:685- 693.
[48] Rubin CS, Hirsch A, Fung C. et al. Development of hormone receptors and hormonal responsiveness in vitro. Insulin receptors and insulin sensitivity in the preadipocyte and adipocyte forms of 3T3-L1 cells[J]. J Biol Chem. 1978. 253:7570-7578.
[49] Nixon T, Green H. Properties of growth hormone receptors in relation to the adipose conversion of 3T3 cells[J]. J Cell Physiol. 1983.115:291-296.
[50] Morikawa M, Green H, Lewis UJ. Activity of human growth hormone and related polypeptides on the adipose conversion of 3T3 cells[J]. Mol Cell Biol. 1984. 4:228-231.
[51] Wang J,Zhou J,Bondy CA. IGF-I promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy[J].FASEB J.1999.13:1985-1990.
[52] Lupu F, Kaechoong L, Segro GV, et al. Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth[J]. Dev Biol. 2001.229:141-162.
[53] S.A.Kaplan, P.Cohen. REVIEW: The Somatomedin Hypothesis 2007: 50 Years Later[J]. The Journal of Clinical Endocrinology & Metabolism. 2007.92(12):4529-4535.
[54] Guevara-Aguirre J RA, Vasconez O, Martinez V. et al. Two year treatment of growth hormone (GH)receptor deficiency with recombinant insulin-like growth factor-1 in 22 children: comparison of two dosage levels and to GH-treatedGHdeficiency[J]. J Clin Endocrinol Metab. 1997.82:629-633.
[55] Ranke MB, Chatelain PG, Preece MA. et al. Long-term treatment of growth hormone insensitivity syndrome with IGF-I. Results of the European Multicentre Study. The Working Group on Growth Hormone Insensitivity Syndromes[J]. Horm Res. 1999. 51:128-134.
[56] LeRoith D, Yakar S, Liu JL. et al. The Somatomedin Hypothesis 2001 [J]. Endocrine Reviews. 2001.22(1):53-74.
[57] Daughaday W H, Hall K, Raben M S. et al. Somatomedin: a proposed designation for the sulfation factor[J]. Nature. 1972.235:107.
[58] Froesch ER, Burgi H, Ramseier EB, et al. Antibodysuppressible and nonsuppressible insulin-like activities in human serum and their physiologic significance. An insulin assay with adipose tissue of increased precision and specificity[J]. J Clin Invest 1963.42:1816-1834.
[59] Rinderknecht E, Humbel RE. Polypeptides with nonsuppressible insulin-like and cell-growth promoting activities in human serum: isolation, chemical characterization,and some biological properties of forms I and II[J]. Proc Natl Acad Sci USA. 1976. 73:2365-2369.
[60] Rotwein P. Structure, evolution, expression and regulation of insulin-like growth factors I and II[J].Growth Factors. 1991. 5:3-18.
[61] Sandra D. O'Dell,Ian N. M. Day. Molecules in focus Insulin-like growth factor II (IGF-II) [J]. The International Journal of Biochemistry & Cell Biology. 1998. 30(7):767-771.
[62] W.Engstr(?)m,A. Shokrai,K.Otte. et al. Transcriptional regulation and biological significance of the insulin like growth factor II gene[J]. Cell Proliferation. 1998. 31(5): 173-189.
[63] Shili Zhan, Lijuan Zhang, Marcus Van, et al. Biallelic expression of all four IGF-II promoters and its association with increased methylation of H19 gene in human brain Brain Research[J]. 1998.792(2):283-290
[64] AV Lallemand, PM Joly, DA Gaillard, et al. In vivo localization of the insulin-like growth factors I and II (IGF I and IGF II) gene expression during human lung development[J]. Int J Dev Biol. 1995.39(3):529-537.
[65] Lopez MF, Dikkes, P,Zurakowski, et al. Regulation of hepatic glycogen in the insulin-like growth factor II-deficient mouse[J]. Endocrinology. 1999. 140(3):1442-1448.
[66] K Malhotra, LL Costello, TJ Raich, et al. Identification of differentially expressed mRNAs in human fetal liver across gestation[J]. Nucleic Acids Research. 1999. 27(3):839-847.
[67] Birnbacher Robert AG, Breitschopf Helene,Lassmann Hans. Et al. Cellular Localization of Insulin-Like Growth Factor II mRNA in the Human Fetus and the Placenta: Detection with a Digoxigenin-Labeled cRNA Probe and Immunocytochemistry[J]. Pediatric Research. 1998.43(5):614-620.
[68] Verhaeghe, Johan, Van Bree. et al. C-Peptide, Insulin-Like Growth Factors I and II, and Insulin-Like Growth Factor Binding Protein-1 in Umbilical Cord Serum: Correlations With Birth Weight[J]. American Journal of Obstetrics and Gynecology. 1993. 169(1):89-97.
[69] S Halvorsen,AG Bechensteen, Physiology of erythropoietin during mammalian development[J].Acta Paediatrica. 2002. 91(438): 17 - 26.
[70] T. Mushtaq, S. F. Ahmed, C. Farquharson. et al. Insulin-Like Growth Factor-I Augments Chondrocyte Hypertrophy and Reverses Glucocorticoid-Mediated Growth Retardation in Fetal Mice Metatarsal Cultures[J]. Endocrinology. 2004. 145(5):2478-2486.
[71] Vander EB, Karperien M. Systemic and regulation of the growth plate[J]. Endocr Rev. 2003.24(6):782-801.
[72] Wang J,Zhou J,Bondy CA. et al. IGF-I promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy[J]. The FASEB Journal. 1999.13(14):1985-1990.
[73] Andrea Giustina GM, Ernesto Canalis. Growth Hormone, Insulin-Like Growth Factors, and the Skeleton[J]. Endocrine Reviews. 2008. 29(5):535-559.
[74] Michele R. Hutchison M, Perrin C. et al. Insulin-Like Growth Factor-I and Fibroblast Growth Factor, But Not Growth Hormone, Affect Growth Plate Chondrocyte Proliferation[J].Endocrinology. 2007. 148(7):3122-3130.
[75] Floria Lupua, Kaechoong Leec,Gino V. et al. Roles of Growth Hormone and Insulin-like Growth Factor 1 in Mouse Postnatal Growth[J]. Developmental Biology. 2001. 229:141-162.
[76] S.Mohan, R. Guo, Y. Amaar, et al. Insulin-Like Growth Factor Regulates Peak Bone Mineral Density in Mice by Both Growth Hormone-Dependent and -Independent Mechanisms[J].Endocrinology. 2003.144(3):929 - 936.
[77] Yuan Song YU, Zheng Bin HAN,Wei LI, et al. Apoptosis in Granulosa cells during follicular atresia: relationship with steroids and insulin-like growth factors[J]. Cell Research. 2004.14:341-346.
[78] Nuttinck F, Mermillod P, Loosfelt H, et a. Expression of components of the insulinlike growth factor system and gonadotropin receptors in bovine cumulus-oocyte complexes during oocyte maturation[J]. Domestic Animal Endocrinology. 2004.27:179-195.
[79] Sudo N, Kawashima C, Kaneko E, et al. Insulin-like growth factor-I (IGF-I) system during follicle development in the bovine ovary: relationship among IGF-I, type 1 IGF receptor (IGFR-1) and pregnancy-associated plasma protein-A (PAPP-A) [J]. Molecular and Cellular Endocrinology. 2007.264:197-203.
[80] Wasielak M. Apoptosis inhibition by insulin-like growth factor (IGF)-I during in vitro maturation of bovine oocytes[J]. Journal of Reproduction and Development 2007. 53:419-426.
[81] H C Liu, Y X Tang, C A Mele, et al. Simultaneous detection of multiple gene expression in mouse and human individual preimplantation embryos[J]. Fertil Steril. 1997. 674:733-741.
[82] Austin EJ, Evans ACO, Knight PG et al. Alterations in intrafollicular regulatory factors and apoptosis during selection of follicles in the first follicular wave of the bovine estrous cycle[J].Biology of Reproduction. 2001. 64:839-848.
[83] Nicholas B, Armstrong DG, Webb R, et al. Changes in insulin-like growth factor binding protein (IGFBP) isoforms during bovine follicular development[J]. Reproductioa 2002. 124:439-446.
[84] Shabrine S. Daftary.Andrea C. Gore, et al. IGF-1 in the Brain as a Regulator of Reproductive Neuroendocrine Function[J]. Experimental Biology and Medicine. 2005. 230:292-306.
[85] JK Hiney, CL Nyberg, SR Ojeda. et al. Insulin-like growth factor I of peripheral origin acts centrally to accelerate the initiation of female puberty[J]. Endocrinology. 1996. 137:3717-3728.
[86] Wison M. E. Premature elevation in serum insulin-like growth faetor-I advances forst ovulation in rhesus monkeys[J]. Journal of Endocrinology. 1998.158:247-257.
[87] CL Adam, PA Findlay, DC Wathes. et al. IGF-I stimulation of luteinizing hormone secretion,IGF-binding proteins (IGFBPs) and expression of mRNAs for IGFs, IGF receptors and IGFBPs in the ovine pituitary gland[J]. Journal of Endocrinology. 2000.166:247-254
[88] M D Ashworth, D R Stein, D T Allen, et al. Endocrine disruption of uterine insulin-like growth factor expression in the pregnant gilt. Reproduction[J]. 2005. 130:545-551.
[89] Cerro, J. A.Pintar, J. E. Insulin-like growth factor binding protein gene expression in the pregnant rat uterus and placenta[J]. Dev Biol. 1997.184(2):278-295.
[90] N.R Nayaka,L.C Giudice. Comparative Biology of the IGF System in Endometrium, Decidua, and Placenta, and Clinical Implications for Foetal Growth and Implantation Disorders[J]. Placenta.2003.24(4):281-296
[91] Dehnhard MC, R.Munz, O.Weiler, et al. Course of epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) in mammary secretions of the goat during end-pregnancy and early lactation[J]. J Vet Med A Physiol Pathol Clin Med 2000. 47(9):533-540.
[92] D.J.Flinta, E. Tonnera,C.J. Wildea, et al. Insulin-like growth factor binding proteins initiate cell death and extracellular matrix remodeling in the mammary gland[J]. Domestic Animal Endocrinology. 2005.29(2):274-282
[93] Lewitt M S, Saunders H, Phuyal J L, et al. Complex formation by human insulin-like growth factor-binding protein-3 and human acid-labile subunit in growth hormone-deficient rats[J].Endocrinology. 1994.134:2402-2409.
[94] Kanety H, Karasik A, Klinger B, et al. Long-term treatment of Laron type dwarfs with insulin-like growth factor I increases serum insulin-like growth factor-binding protein 3 in the absence of growth hormone activity[J].Acta Endocrinol. 1993. 128:144-159.
[95] Leal SM, Huang SS, Huang JS. et al. Interactions of high affinity insulin-like growth factor-binding proteins with the type V transforming growth factor-b receptor in mink lung epithelial cells[J]. J Biol Chem. 1999.274:6711-6717.
[96] Reinecke M, Collet C. The phylogeny of the insulin-like growth factors[J]. Int Rev Cytol. 1998. 183:1-94.
[97]Vivian Hwa,Youngman Oh,Ron G.Rosenfeld.The Insulin-Like Growth Factor-Binding Protein (IGFBP) Superfamily[J].Endocrine Reviews.1999.20(6):761-787.
[98]Neumann G,Bach L.The N-terminal disulfide linkages of human insulin-like growth factor-binding protein-6(hIGFBP-6) and hIGFBP-1 are different as determined by mass spectrometry[J].J Biol Chem.1999.274:14587-14594.
[99]Hashimoto R,Fujiwara H,Higashihashi N,et al.Binding sites and binding properties of binary and ternary complexes of insulin-like growth factor-Ⅱ(IGF-Ⅱ),IGF-binding protein-3,and acid-labile subunit[J].J Biol Chem.1997.272:27936-27942.
[100]Zapf J,Chang JY,James P,et al.Isolation and NH2-terminal amino acid sequences of rat serum carrier proteins for insulin-like growth factors[J].Biochem Biophys Res Commun.1988.156:1187-1194.
[101]Ceda G P,Henzel W J,Louie A,et al.Differential effects of insulin-like growth factor(IGF)-Ⅰ and IGF-Ⅱ on the expression of IGF binding proteins(IGFBPs) in a rat neuroblastoma cell line:isolation and characterization of two forms of IGFBP-4[J].Endocrinology.1991.128:2815-2824.
[102]Claussen M,Schuller AG,Matzner U,et al.Regulation of insulin-like growth factor(IGF)-binding protein-6 and mannose 6-phosphate/IGF-Ⅱ receptor expression in IGF-IL-overexpressing NIH 3T3cells[J].Mol Endocrinol.1995.9:902-912.
[103]Westwood M,White A.Purification and characterization of the insulin-like growth factor-binding protein-1 phosphoform found in normal plasma[J].Endocrinology.1997.138:1130-1136.
[104]Jones JI,Wright G,Smith CE,et al.Identification of the sites of phosphorylation in sinulin-like growth factor binding protein-1:regulation of its affinity by phosphorylation of serinel01[J].J Biol Chem.1993.268:1125-1131.
[105]Coverley JA.Regulation of insulin-like growth factor(IGF) binding protein-3 phosphorylation by IGF-Ⅰ[J].Endocrinology.1995.136:5778-5781.
[106]Thompson JD,Gibson TJ.CLUSTAL W:improving the sensitivity of progressive multiple sequence alignment through sequence weighting,position-specific gap penalties and weight matrix choice[J].Nucleic Acids Research.1994.22(4673-4680).
[107]Forbes B E,Hodge S J,McNeil K A,et al.Localization of an insulin-like growth factor(IGF)binding site of bovine IGF binding protein-2 using disulfide mapping and deletion mutation analysis of the C-terminal domain[J].J Biol Chem.1998.273:4647-4652.
[108]Malthiery Y,Lissitzky S.Primary structure of human thyroglobulin deduced from the sequence of its 8448-base complementary DNA[J].Eur J Biochem.1987.165:491-498..
[109]Sala AC,S.Campagnoli,M.Faggion,et al.Structure and properties of the C-terminal domain of insulin-like growth factor-binding protein-1 isolated from human amniotic fluid[J].J Biol Chem.2005.280(33):29812-29819.
[110]Fowlkes JL,George-Nascimento C,Rosenberg CK,et al.Heparin-binding,highly basic regions within the thyroglobulin type-Ⅰ repeat of insulin-like growth factor(IGF)-binding protleins (IGFBPs) -3,-5,and -6 inhibit IGFBP-4 degradation.Endocrinology[J].1997.138:2280-2285.
[111]Kuang ZY,S.McNeil,K.A.Thompson,et al.Cooperativity of the N- and C-terminal domains of insulin-like growth factor(IGF) binding protein 2 in IGF binding[J].Biochemistry.2007.46(48):13720-13732.
[112]Zhihe Kuang,David W.Keizer,Chunxiao C.et al.Structure,Dynamics and Heparin Binding of the C-terminal Domain of Insulin-like Growth Factor-binding Protein-2(IGFBP-2)[J].Journal of Molecular Biology. 2006. 364(4):690-704
[113]R. Rajah, B. Valentinis, P. Cohen, et al. Insulin-like growth factorbinding proteins in serum and other biological fluids: regulation and functions[J]. Endocr Rev. 1997.18:801-831.
[114]Qin X, Baylink DJ, Mohan S. et al. Structure-function analysis of the human insulin-like growth factor binding protein-4[J]. J Biol Chem. 1998. 273:23509-23516.
[115]Imai Y, Smith CE, Clarke JB, et al. Protease-resistant form of insulin-like growth factor-binding protein 5 is an inhibitor of insulinlike growth factor-I actions on porcine smooth muscle cells in culture[J]. J Clin Invest 1997. 100:2596-2605.
[116]Bramani S, Beattie J, Tonner E, et al. Amino acids within the extracellular matrix (ECM) binding region (201-218) of rat insulin-like growth factor binding protein (IGFBP-5) are important determinants in binding IGF-I. J Mol Endocrinol. 1999.23:117-123.
[117]Iosef CG, T.Jia, C. Y.Li, et al. A functional nuclear localization signal in insulin-like growth factor binding protein-6 mediates its nuclear import[J]. Endocrinology. 2008. 149(3): 1214-1226.
[118]Oh Y MH, Lamson G, Rosenfeld RG. Insulin-like growth factor (IGF)-independent action of IGF-binding protein-3 in Hs578T human breast cancer cells. J Biol Chem. 1993.268:14964-14971.
[119]Fu, P.Thompson, J. A.Bach, L. A. Promotion of cancer cell migration: an insulin-like growth factor (IGF)-independent action of IGF-binding protein-6[J]. J Biol Chem. 2007. 282(31):22298-22306.
[120]Kalus W, Renner C, SanchezY, et al. Structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions[J].EMBO J. 1998. 17:6558-6572.
[121]Sara V, Andersson C, Hall E, et al. Characterization of somatomedins from human fetal brain:identification of a variant form of insulin-like growth factor I[J]. Proc Natl Acad Sci USA. 1986.83:4904-4907.
[122]Forbes B, Baxter RC, Ballard FJ, et al. Classification of the insulin-like growth factor binding proteins into three distinct categories according to their binding specificities[J]. Biochem Biophys Res Commua 1988.157:196-202.
[123]Clemmons DR, Camacho-Hu bner C, Mc-Cusker RH, et al. Discrete alterations of the insulin-like growth factor I molecule which alter its affinity for insulin-like growth factor-binding proteins result in changes in bioactivity[J]. J Biol Chem. 1990.265:12210-12216.
[124]Bach LA, Sakano K, Fujiwara H, et al. Binding of mutants of human insulin-like growth factor II to insulin-like growth factor binding proteins 1-6[J]. J Biol Chem. 1993.268:9246-9254.
[125]Baxter RC. Insulin-like growth factor (IGF)-binding proteins:interactions with IGFs and intrinsic bioactivities[J]. Am J Physiol Endocrinol Metab. 2000. 278:967-976.
[126]Vorwerk P, Spagnoli A, Oh Y, et al. Insulin and IGF binding by IGFBP-3 fragments derived from proteolysis, baculovirus expression and normal human urine[J]. J Clin Endocrinol Metab. 1998.83:1392-1395.
[127]Hobba GD, Holmberg E, Forbes BE, et al. Alanine screening mutagenesis establishes tyrosine 60 of bovine insulin-like growth factor binding protein-2 as a determinant of insulin-like growth factor binding[J]. J Biol Chem. 1998. 273:19691-19698.
[128]Qin X, Baylink D J, Mohan S. Structurefunction analysis of the human insulin-like growth factor binding protein-4. J Biol Chem. 1998. 273:23509-23516.
[129]Imai Y, Clarke J B, Busby W, et al. Synthesis and characterization of IGFBP-5 and IGFBP-3 mutants that have no affinity for IGF-I[J]. GH and IGF Res. 1999. 9:372.
[130]Firth S M, Baxter R C. Structural determinants of ligand and cell-surface binding of insulin-like growth factor-binding protein-3[J]. J Biol Chera 1998. 273:2631-2638.
[131]Jones J I, Camacho H C, Clemmons D R, et al. Phosphorylation of insulin-like growth factor (IGF)-binding protein 1 in cell culture and in vivo: effects on affinity for IGF-I[J]. Proc Natl Acad Sci USA. 1991.88:7481-7485.
[132]Frystyk J, Skj(?)rbask C, (?)rskov H. The effect of oral glucose on serum free insulin-like growth factor-I and -II in healthy adults[J]. J Clin Endocrinol Metab. 1997. 82:3124-3127.
[133]Ho P J,Baxter R C. Characterization of truncated insulinlike growth factor-binding protein-2 in human milk[J]. Endocrinology. 1997. 138:3811-3818.
[134]Lalou C, Lassarre C, Binoux M. A. et al. proteolytic fragment of insulin-like growth factor (IGF) binding protein-3 that fails to bind IGFs inhibits the mitogenic effects of IGF-I and insulin[J].Endocrinology. 1996. 137:3206-3212.
[135]Lassarre C,Binoux M. et al. Insulin-like growth factor binding protein-3 is functionally altered in pregnancy plasma[J]. Endocrinology. 1994. 134:1254-1262.
[136]Baxter R C.Skriver L. Altered ligand specificity of proteolysed insulin-like growth factor binding protein-3[J]. Biochem Biophys Res Commun. 1993.196:1267-1273.
[137]J.I. Jones, W.H. Busby, G Wright, et al. Insulin-like growth factor binding protein1 stimulates cell migration and binds to the a5bl integrin by means of its Arg-Gly-Asp sequence[J]. Proc Natl Acad Sci USA. 1993. 90. 10553-10557.
[138]L.M. Gleeson, C. Chakraborty, T. McKinnon. et al. Insulinlike growth factor-binding protein1 stimulates human trophoblast migration by signaling through alpha 5 beta1 integrin via mitogenactivated protein Kinase pathway[J]. J Clin Endocrinol Metab. 2001, 86 2484-2493.
[139]C.M. Perks, P.V. Newcomb, M.R. Norman, et al. Effect of insulin-like growth factor binding protein-1 on integrin signaling and the induction of apoptosis in human breast cancer cells[J]. J Mol Endocrinol. 1999.22:141-150.
[140]J.M. Ricort, M. Binoux. Insulin-like growth factor binding protein (IGFBP) signalling[J]. Growth Hormone & IGF Research. 2004. 14 277-286.
[141]J.I. Leu, M.A. Crissey, R. Taub. Massive hepatic apoptosis associated with TGF-beta 1 activation after Fas ligand treatment of IGF binding protein-1-deficient mice[J]. J Clin Invest 2003.111:129-139.
[142]Shahjee HB, N.Zappala, GWiench, et al. An N-terminal fragment of insulin-like growth factor binding protein-3 (IGFBP-3) induces apoptosis in human prostate cancer cells in an IGF-independent manner[J]. Growth Horm IGF Res. 2008. 18 (3 ):188-197.
[143]L.Buckbinder, S. Velasco-Miguel, I. Takenaka, et al. Induction of the growth inhibitor IGF-binding protein 3 by p53[J]. Nature. 1995. 377:644-649.
[144]T. Nickerson, H. Huynh, M. Pollak. Insulin-like growth factor binding protein-3 induces apoptosis in MCF7 breast cancer cells[J]. Biochem Biophys Res Commua 1997. 237:690-693.
[145]C.M.Perks, Z.P.Gill, P.V.Newcomb, et al. Differential IGF-independent effects of insulin-like growth factor binding proteins (1-6) on apoptosis of breast epithelial cells[J]. JCell Biochem. 1999.75:652-664.
[146]A. Butt, M. King, R. Baxter, et al. Insulin-like growth factorbinding protein-3 modulates expression of Bax and Bcl-2 and potentiates p53-independent radiation-induced apoptosis in human breast cancer cells[J]. J Biol Chem. 2000, 275:39174-39181.
[147]A.C. Williams, CM. Perks, P. Newcomb, et al. Increased p53-dependent apoptosis by the insulin-like growth factor binding protein IGFBP-3 in human colonic adenoma-derived cells[J].Cancer Res. 2000.60:22-27.
[148]R. Rajah, B. Valentinis, P. Cohen. Insulin-like growth factorbinding protein-3 induces apoptosis and mediates the effects of transforming growth factor-b1 on programmed cell death through a p53-and IGF-independent mechanism[J]. J Biol Chem. 1997.272:12181-12188.
[149]A. Spagnoli, S.R. Nagalla, W.A. Horton, et al. Identification of STAT-1 as a molecular target of IGFBP-3 in the process of chondrogenesis[J]. J Biol Chem. 2002. 277:18860-18867.
[150]S.E. Damon, J.L. Ware, S.R. Plymate. et al. Overexpression of an inhibitory insulin-like growth factor binding protein (IGFBP), IGFBP-4, delays onset of prostate tumor formation[J].Endocrinology 1998. 139:3456-3464.
[151JR.H. Drivdahl, K. Trimm, S.R. Plymate, et al. Inhibition of growth and increased expression of insulin-like growth factorbinding protein-3 (IGFBP-3) and -6 in prostate cancer cells stably transfected with antisense IGFBP-4 complementary deoxyribonucleic acid[J]. Endocrinology 2001.142:1990-1998.
[152]A.J. Butt, F. McDougall, R.C. Baxter, et al. Insulin-like growth factor-binding protein-5 inhibits the growth of human breast cancer cells in vitro and in vivo[J].J Biol Chem.2003.278:29676-29685.
[153]B. Liu, S. Weinzimer, D. Powell, et al. Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-alpha regulate transcriptional signaling and apoptosis[J]. J Biol Chem. 2000. 275:33607-33613.
[154]Y.G Amaar, T.A. Linkhart, S.T. Chen, et al. Insulin-like growth factor-binding protein5 (IGFBP-5) interacts with a four and a half LIM protein 2 (FHL2) [J]. J Biol Chem. 2002.277:12053-12060.
[155]L.J. Schedlich, G.M. Leong, R.C. Baxter, et al. Insulin like growth factor binding protein-3 prevents retinoid receptor heterodimerization: implications for retinoic acid-sensitivity in human breast cancer cells[J]. Biochem Biophys Res Commua 2004. 314:83-88.
[156]S. Fanayan, A.J. Butt, R.C. Baxter, et al. Growth inhibition by insulin-like growth factor-binding protein-3 in T47D breast cancer cells requires transforming growth factor-beta (TGF-beta) and the type II TGF-beta receptor[J]. J Biol Chem. 2000. 275:39146-39151.
[15]S. Fanayan, S.M. Firth, R.C. Baxter. Signaling through the Smad pathway by insulin-like growth factor-binding protein-3 in breast cancer cells. Relationship to transforming growth factor-beta 1 signaling[J]. J Biol Chem. 2002. 277:7255-7261.
[158]R. Oklu, R. Hesketh. The latent transforming growth factor beta binding protein (LTBP) family[J].Biochem J. 2000. 352 (Pt 3):601-610.
[159]Y. Gui, L.J. Murphy. Interaction of insulin-like growth factor binding protein-3 with latent transforming growth factor-beta binding protein-1[J]. Mol Cell Biochem. 2003. 250:189-195.
[160]J.L. Martin, R.C. Baxter. Oncogenic ras causes resistance to the growth inhibitor insulin-like growth factor binding protein-3 (IGFBP-3) in breast cancer cells[J]. J Biol Chem. 1999.274:16407-16411.
[161]J.L. Martin, S.M. Weenink, R.C. Baxter. Insulin-like growth factor-binding protein-3 potentiates epidermal growth factor action in MCF-10A mammary epithelial cells. Involvement of p44/42 and p38 mitogen-activated protein kinases[J]. J Biol Chem. 2003. 278 2969-2976.
[162]C.A. Conover, S.K. Durham, D.R. Powell, et al. Insulin-like growth factor (IGF) binding protein-3 potentiation of IGF action is mediated through the phosphatidylinositol-3-kinase pathway and is associated with alteration in protein kinase B/AKT sensitivity[J]. Endocrinology. 2000. 141:3098-3103.
[163]J.M. Ricort, M. Binoux. Insulin-like growth factor binding protein-3 stimulates phosphatidylinositol 3-kinase in MCF-7 breast carcinoma cells[J]. Biochem Biophys Res Commun.2004.314 1044-1049.
[164]J.M. Ricort, M. Binoux. Insulin-like growth factor-binding protein-3 activates a phosphotyrosine phosphatase. Effects on the insulin-like growth factor signaling pathway[J]. J Biol Chem. 2002.277:19448-19454.
[165]J.M. Ricort, M. Binoux. Insulin-like growth factor binding protein-3 inhibits type 1 insulin-like growth factor receptor activation independently of its insulin-like growth factor binding affinity[J].Endocrinology. 2001. 142 108-113.
[166]Kato H, Faria TN, Stannard B, et al. Essential role of tyrosine residues 1131, 1135,and 1136 of the insulin-like growth factor-I (IGF-I) receptor in IGF-I action. Mol Endocrinology. 1994. 8:40-50.
[167]LeRoith D, Werner H, Beitner-Johnson D, et al. Molecular and cellular aspects of the insulin-like growth factor I receptor[J]. Endocr Rev. 1995. 16:143-163.
[168]Y Yang, J Niu,L Guo. The effects of antisense insulin-like growth factor-I receptor oligonucleotide on human cord blood lymphocytes. Journal of Molecular[J] Endocrinology. 2002. 28(3):207-212.
[169]Bondy CA,Werner H, Roberts CT, Jr, et al. Cellular pattern of insulin-like growth factor I (IGF-I) and type I IGF receptor gene expression in early organogenesis: comparison with IGF-II gene expression[J]. Mol Endocrinol. 1990.4:1386-1398.
[170]kornfeld s. Structure and function of the mannose 6-phosphate/insulinlike growth factor II receptors[J]. Annu Rev Biochem. 1992., 61:307-330.
[171]M J Ellis,BA Leav,Z Yang,et al. Affinity for the insulin-like growth factor-II (IGF-II) receptor inhibits autocrine IGF-II activity in MCF-7 breast cancer cells[J]. Molecular Endocrinology. 1996.10:286-297.
[172]Zhihong Chen,Yinlin Ge,Jing X Kang. Down-regulation of the M6P/IGF-II receptor increases cell proliferation and reduces apoptosis in neonatal rat cardiac myocytes[J]. BMC Cell Biology. 2004.5(15):1-12.
[173]Jawon Seo,Kong-Joo Lee. Post-translational Modifications and Their Biological Functions:Proteomic Analysis and Systematic Approaches[J]. Journal of Biochemistry and Molecular Biology.2004. 37(1):35-44.
[174]Ficarro S B, McCleland M L, Stukenberg P T. Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nature Biotechnology. 2002.20(3):301-305.
[175]Krupa A, Preethi G, Srinivasan N. Structural modes of stabilization of permissive phosphorylation sites in protein kinases:distinct strategies in Ser/Thr and Tyr kinases[J]. J Mol Biol. 2004.339:1025-1039.
[176]Fowler D, Albaiges, G, Lees, C, Jones, J.,et al. The role of insulin-like growth factor binding protein-1 phosphoisoforms in pregnancies with impaired placental function identified by doppler ultrasound[J]. Hum Reprod. 1999. 14:2881-2885.
[177]Yu J, Iwashita, M., Kudo, Y.,et al. Phosphorylated insulin-like growth factor(IGF)-binding protein-1 (IGFBP-1) inhibits while non-phosphorylated IGFBP-1 stimulates IGF-Iinducedamino acid uptake by cultured trophoblast cells[J]. Growth Horm IGF Res. 1998. 8:65-70.
[178]Gibson JM, Aplin J. D., White, A., et al. Regulation of IGF bioavailability in pregnancy[J]. Mol Hum Reprod. 2001. 7:79-87.
[179]Nissum MA, M.Sukop, U.Khosravi, et al. Functional and complementary phosphorylation state attributes of human insulin-like growth factor binding protein-1( IGFBP-1) isoforms resolved by free flow electrophoresis[J]. Mol Cell Proteomics. 2009.
[180]Seferovic M, R.Kamei, H.Liu, et al. Hypoxia and leucine deprivation induce human insulin-like growth factor binding protein-1 hyperphosphorylation and increase its biological activity[J].Endocrinology. 2009. 150(1):220-231.
[181]Graham M, D. M.Firth, S. M.Robinson, et al. The in vivo phosphorylation and glycosylation of human insulin-like growth factor-binding protein-5[J]. Mol Cell Proteomics. 2007. 6120(8):1392-1405.
[182]Schedlich L, T.John, A. P.Jans, et al. Phosphorylation of insulin-like growth factor binding protein-3 by deoxyribonucleic acid-dependent protein kinase reduces ligand binding and enhances nuclear accumulation[J]. Endocrinology. 2003. 144(5): 1984-1993.
[183]Blom N, Sicheritz-Ponten T, Gupta R. Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence[J]. Proteomics. 2004.4:1633-1649.
[184]Gavel Y, von Heijne G. Statistical studies of N-glycosylated proteins have indicated that the frequency of nonglycosylated Asn-Xaa-(Thr/Ser) sequons increases toward the C terminus[J].Protein Eng. 1990,3:433-442.
[185]Marinaro J, G. M.Russo, V. C.Leeding, K. S. et al. O-glycosylation of insulin-like growth factor (IGF) binding protein-6 maintains high IGF-II binding affinity by decreasing binding to glycosaminoglycans and susceptibility to proteolysis[J]. Eur J Biochem. 2000.267(17):5378-5386.
[186]Firth, S. M.Baxter, R. C. Characterisation of recombinant glycosylation variants of insulin-like growth factor binding protein-3[J]. J Endocrinol. 1999.160(3):379-387.
[187]Igor Siwanowicz, Magdalena Wisniewska. Structural Basis for the Regulation of Insulin-like Growth Factors by IGF Binding Proteins[J]. Structure. 2005.13:155-167.
[188]Payet LD, Wang, X.H., Baxter, R.C., et al. Amino and carboxyl-terminal fragments of insulin-like growth factor (IGF)binding protein-3 cooperate to bind IGFs with high affinity and inhibit IGF receptor interactions[J]. Endocrinology. 2003. 144: 2797-2806.
[189]Shand JH, Beattie, J., Song, H., et al. Specific amino acid substitutions determine the differential contribution of the N- and C-terminal domains of insulin-like growth factor (IGF)-binding protein-5 in binding IGF-I[J]. J Biol Chem. 2003.278(17859-17866).
[190]Buckway CK, Wilson, E.M., Ahlsen, M.,et al. Mutation of three critical amino acids of the N-terminal domain of IGF-binding protein-3 essential for high affinity IGF binding[J]. J Clin Endocrinol Metab. 2001. 86:4943-4950.
[191]Buel D. Rodgers, Cullen Thompson. Phylogenetic analysis of the insulin-like growth factor binding protein (IGFBP) and IGFBP-related protein gene families[J]. General and Comparative Endocrinology. 2008. 155:201-207.
[192]Jones JL, Doerr ME. Cell migration: interactions among integrins, IGFs and IGFBPs[J]. Prog Growth Factor Res. 1995. 6:319-327.
[193]Vandesompele J, De Preter K, Pattyn F, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes[J]. Genome Biol. 2002.3(7):34-42.
[194]Lee RS, Depree KM, Davey HW. The sheep (Ovis aries) H19 gene:genomic structure and expression patterns, from the preimplantation embryo to adulthood[J]. Gene. 2002. 301:67-77.
[195]Todorovic VP, P.Micev, M.Bjelovic, et al. Insulin-like growth factor-I in wound healing of rat skin[J]. Regul Pept 2008. 150(1-3):7-13.
[196]Joseph D'Ercole, A.Ye, P. Expanding the mind: insulin-like growth factor I and brain development[J]. Endocrinology. 2008.149(12):5958-5962.
[197]Ruo L. Chen NAK, Mahvand Sadeghi, et al. Insulin-Like Growth Factor-II Uptake Into Choroid Plexus and Brain of Young and Old Sheep[J]. Journal of Gerontology. 2008. 63(2): 141-148.
[198]Chowen J, L.Ramos, S.Busiguina, et al. Effects of early undernutrition on the brain insulin-like growth factor-I system[J]. J Neuroendocrinol. 2002.14(2):163-169.
[199]Cheng C, R. R.Lee, W. H.Joncas, et al. Insulin-like growth factor 1 regulates developing brain glucose metabolism[J]. ProcNatl Acad Sci U S A. 2000.97(18):10236-10241.
[200]Werther G, V.Baker, N.Butler, et al. The role of the insulin-like growth factor system in the developing brain[J]. Horm Res. 1998.49 (Suppl 1):37-40.
[201]Ye, P.D'Ercole, J. Insulin-like growth factor I (IGF-I) regulates IGF binding protein-5 gene expression in the brain[J]. Endocrinology. 1998. 139(1):65-71.
[202]Yasuoka HL, A. T.Yamaguchi, Y.Feghali-Bostwick, et al. Human skin culture as an ex vivo model for assessing the fibrotic effects of insulin-like growth factor binding proteins[J]. Open Rheumatol J.2008.2:17-22.
[203]Reijnders C, N.HoIzmann, P. J.Bhoelan, et al. In vivo mechanical loading modulates insulin-like growth factor binding protein-2 gene expression in rat osteocytes[J]. Calcif Tissue Int 2007.80(2):137-143.
[204.]R. L.Mamabolo, N. S.Levitt, H. A.Delemarre-van de Waal, et al. Association between insulin-like growth factor-1, insulin-like growth factor-binding protein-1 and leptin levels with nutritional status in 1-3-year-old children, residing in the central region of Limpopo Province, South Africa[J].Br J Nutr. 2007. 98(4):762-769.
[205]Lelbach, A.Scharf, J. G.Ramadori, G. Regulation of insulin-like growth factor-I and of insulin-like growth factor binding protein-1, -3 and -4 in cocultures of rat hepatocytes and Kupffer cells by interleukin-6[J]. J Hepatol. 2001. 35(5):558-567.
[206]Kamangar, B. B.Gabillard, J. C.Bobe, J. Insulin-like growth factor-binding protein (IGFBP)-1, -2,-3, -4, -5, and -6 and IGFBP-related protein 1 during rainbow trout postvitellogenesis and oocyte maturation: molecular characterization, expression profiles, and hormonal regulation[J].Endocrinology. 2006. 147(5):2399-2410.
[207]Stephens M, Smith N, Donnelly P. A new statistical method for haplotype reconstruction from population data. American Journal of Human[J] Genetics. 2001. 68:978-989.
[208]T Noumi, S Natori,M Futai, et al. A phenylalanine for serine substitution in the beta subunit of Escherichia coli F1-ATPase affects dependence of its activity on divalent cations[J]. J Biol Chem.1984. 259(16): 10071-10075.
[209]M Orita HI, H Kanazawa,K Hayashi, et al. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms[J]. Proc Natd Acad Sci USA. 1989.86 (8):2766-2770.
[210]Orita M, Sekiya T,Hayashi K. et al. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction[J]. Genomics. 1989.5(4):874-879.
[211]Hoshino S, Fukuda Y,Dohi K,Sasazuki T, et al. Polymerase chain reaction-single-strand conformation polymorphism analysis of polymorphism in DPA1 and DPB1 genes: a simple,economical, and rapid method for histocompatibility testing[J].Hum Immunol. 1992. 33(2):98-107.
[212]Spinardi L, Mazars R, Theillet C. Protocols for an improved detection of point mutation by SSCP[J]. Nucleic Acids Research. 1991. 19(14):4009.
[213]Fu YH, Pizzuti A, Pieretti M, et al. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox[J]. Cell. 1992.67(6): 1047-1058.
[214]Botstein D, Skolnick M, Davis RW, et al. Construction of a genetic linkage map in man using restriction fragment length polymorphism[J]. American Journal of Human Genet 1980.32(3):314-331.
[215]B Dalrymple, E Kirkness, M Nefedov, et al. Using comparative genomics to reorder the human genome sequence into a virtual sheep genome[J].Genome Biology. 2007. 8(7):R152.152-R152.120.
[216]Bennett, A. K.Hester, P. Y.Spurlock, D. E. Polymorphisms in vitamin D receptor, osteopontin,insulin-like growth factor 1 and insulin, and their associations with bone, egg and growth traits in a layer-broiler cross in chickens[J]. Anim Genet 2006. 37(3):283-286.
[217]Johnston L, J.Leger, J.Gelander, et al. Association between insulin-like growth factor I (IGF-I) polymorphisms, circulating IGF-I, and pre- and postnatal growth in two European small for gestational age populations[J]. J Clin Endocrinol Metab. 2003. 88(10):4805-4810.
[218]Zhou HM, A. D.McMurtry, J. P.Ashwell, et al. Insulin-like growth factor-I gene polymorphism associations with growth, body composition, skeleton integrity, and metabolic traits in chickens[J].Poult Sci. 2005.84(2):212-219.
[219]Taylor J, M. J.Bromage, N. R.Migaud, et al. Relationships between environmental changes,maturity, growth rate and plasma insulin-like growth factor-I (IGF-I) in female rainbow trout[J].Gen Comp Endocrinol. 2008.155(2):257-270.
[220]Amills MJ, N.Villalba, D.Tor, et al. Identification of three single nucleotide polymorphisms in the chicken insulin-like growth factor 1 and 2 genes and their associations with growth and feeding traits[J]. Poult Sci. 2003, 82(10):1485-1493.
[221]Maj AS, M.Siadkowska, E.Rowinska, B.Lisowski, et al. Polymorphism in genes of growth hormone receptor (GHR) and insulin-like growth factor-1 (IGF1) and its association with both the IGF1 expression in liver and its level in blood in Polish Holstein-Friesian cattle[J]. Neuro Endocrinol Lett 2008. 29(6):981-989.
[222]Wang GY, B.Deng, X.Li, et al. Insulin-like growth factor 2 as a candidate gene influencing growth and carcass traits and its bialleleic expression in chicken[J]. Sci China C Life Sci. 2005.48(2):187-194.
[223]Savage S, K.Walk, E.Modi, et al. Analysis of genes critical for growth regulation identifies Insulin-like Growth Factor 2 Receptor variations with possible functional significance as risk factors for osteosarcoma[J]. Cancer Epidemiol Biomarkers Prev. 2007. 16(8): 1667-1674.
[2]吴登俊.培育凉山半细毛羊的启示[J].四川草原.2003.4:5-9.
[3]陈圣偶.凉山半细毛羊的选育及其生产性能.草食家畜[J].2002.115(2):19-22.
[4]陈圣偶.李利,张红平等.凉山半细毛羊育成期生长发育的研究[J].四川草原.2002.2:57-60.
[5]李利,陈圣偶.凉山半细毛羊血液生化指标与生产性能的相关性研究[J].四川农业大学学报.2001.19(1):91-93.
[6]姜勋平,陈圣偶,刘相模.凉山半细毛羊遗传结构研究[J].四川农业大学学报.1996.14(3):457-460.
[7]李小晴,吴登俊,陈圣偶.凉山半细毛羊、山谷型藏绵羊Ag-NoRs带的比较研究.四川大学学报(自然科学版)[J].2000.37(增刊):144-147.
[8]李小晴,吴登俊,陈圣偶等.凉山半细毛羊与山谷型藏绵羊染色体核型的比较[J].西北农林科技大学学报(自然科学版).2006.34(12):11-15.[
9]李小晴,吴登俊,陈圣偶等,凉山半细毛羊、山谷型藏绵羊染色体畸变研究[J].畜牧兽医学报.2007.38(4):400-406.
[10]赵俊丽.利用微卫星标记进行凉山半细毛羊羊毛性状的QTL定位研究[M].硕士论文.四川雅安.四川农业大学.2002.
[11]贾兰平.利用微卫星标记进行凉山半细毛羊体重QTL研究[M].硕士论文.四川雅安.四川农业大学.2002.
[12]陈艺.凉山半细毛羊2号染色体遗传连锁框架图的构建及体重性状QTL定位的研究[M]..硕士论文.四川雅安.四川农业大学.2004.
[13]张明娅,吴登俊.凉山半细毛羊1号染色体微卫星遗传连锁图谱的构建[J].遗传.2005.27(4):575-578.
[14]张明娅.凉山半细毛羊1号染色体遗传连锁图和羊毛性状QTL定位研究[M].硕士论文.四川雅安.四川农业大学.2004.
[15]张鹦俊.凉山半细毛羊2号染色体羊毛性状的QTL定位研究[M].硕士论文.四川雅安.四川农业大学.2004.
[16]李辉.凉山半细毛羊QTL定位初步研究[M].博士论文.四川雅安.四川农业大学.2006.
[17]周明亮,吴登俊.绵羊3号染色体的遗传连锁图谱构建及QTL定位[J].遗传.2007.29(12):1475-1482.
[18]高爱保,吴登俊.利用微卫星标记进行凉山半细毛羊亲权鉴定的研究[J].遗传.2005.27(1):85-90.
[19]王高富,吴登俊.凉山半细毛羊微卫星标记与羊毛性状的相关分析[J].遗传.2006.28(12):1505-1512.
[20]张翔宇.凉山半细毛羊微卫星多态性与体重性状的相关分析[M].硕士论文.四川雅安.四川农业大学.2006.
[21]余敏.凉山半细毛羊资源参考群信息数据库的初步构建[M].硕士论文.四川雅安.四川农业大.2007.
[22]姜勋平,陈圣偶.凉山半细毛羊横交群重要经济性状遗传率及其相关分析[J].四川畜牧兽医 1996,1:9-10.
[23]杨平贵,吴登俊.凉山半细毛羊几个早期性状遗传参数的估测[J].畜禽业.2006.192:12-13.
[24]刘阳。凉山半细毛羊主要生产性状的遗传参数评估[M].硕士论文.四川雅安.四川农业大学.2007.
[25]Salmon W D,Daughaday W H,A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro[J].J Lab Clin Med.1957.49:825-826.
[26]Derek Le Roith C.B.,Shoshana Yakar,Jun-li Liu,et al.The Somatomedin Hypothesis:2001[J].Endocrine Reviews.2001.22(1):53-74.
[27]Murphy W R,Daughaday W H,Hartnett C.The effect of hypophysectomy and growth hormone on the incorporation of labeled sulfate into tibila epiphyseal and nasal cartilage of the rat[J].J Lab Clin Med.1956.47:715-722.
[28]Denko CW,Bergenstal DM.The effect of hypophysectomy and growth hormone on cartilage sulfate metabolism[J].Proc Soc Exp Biol Med.1955.84:603-605.
[29]Daughaday W H,Reeder C.Synchronous activation of DNA synthesis in hypophysectomized rat cartilage by growth hormone[J].J Lab Clin Med 1966.68:357-368.
[30]Garland J T LME,Kozak S,Daughaday W H:Stimulation of DNA synthesis in isolated chondrocytes by sulfation factor[J].Endocrinology.1972.90:1086-1090.
[31]Daughaday WH,Hall K,Raben MS,et al.Somatomedin:proposed designation for sulphation factor[J].Nature.1972.235:107.
[32]Klapper D G,Svoboda M E,Van Wyk J J.Sequence analysis of somatomedin-C:confirmation of identity with insulin-like growth factor I[J].Endocrinology.1983.112:2215-2217.
[33]Rinderknecht E,Humbel RE.The amino acid sequence of human insulin-like growth factor Ⅰ and its structural homology with proinsulin[J].J Biol Chem.1978.253:2769-2776.
[34]Randle P J.Plasma-insulin activity in hypopituitarism[J].Lancet 1954.1:809-810.
[35]Blundell T L,Bedarkar S,Rinderknecht E.Insulin-like growth factor:a model for tertiary structure accounting for immunoreactivity and receptor binding[J].Proc Natl Acad Sci.1978.75:180-184.
[36]Blundell TL,Bedarkar S,Humbel RE.Tertiary structures,receptor binding,and antigenicity of insulin-like growth factors[J].Fed Proc.1983.42:2592-2597.
[37]Berelowitz M,Szabo M,Frohman LA.et al.Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary[J].Science.1981.212:1279-1281.
[38]D'Ercole AJ,Applewhite GT,Underwood LE.et al.Evidence that somatomedin is synthesized by multiple tissues in the fetus[J].Dev Biol.1980.75:315-328.
[39]Jansen M,van Schaik FM,Ricker AT.et al.Sequence of cDNAencoding human insulin-like growth factor Ⅰ precursor[J].Nature.1983.306:609-611.
[40]Kajimoto Y,Rotwein P.Structure and expression of a chicken insulin-like growth factor Ⅰprecursor[J].Mol Endocrinol.1989.3:1907-1913.
[41]Lowe Jr WL,Lasky SR,LeRoith D.Distribution and regulation of rat insulin-like growth factor Ⅰmessenger ribonucleic acids encoding alternative carboxy-terminal E-peptides:evidence for differential processing and regulation in liver[J].Mol Endocrinol.1988.2:528-535.
[42]Lowe WL,Roberts Jr CT,Lasky SR.Differential expression of alternative 59 untranslated regions in mRNAs encoding rat insulin-like growth factor I[J].Proc Natl Acad Sci USA.1987.84:8946-8950.
[43]Isaksson OG,Jansson JO,Gause IA.Growth hormone stimulates longitudinal bone growth directly[J].Science.1982.216:1237-1239.
[44] Schlechter NL, Russell SM, Spencer EM. et al. Evidence suggesting that the direct growth-promoting effect of growth hormone on cartilage in vivo is mediated by local production of somatomedin[J]. Proc Natl Acad Sci USA. 1986. 83:7932-7934.
[45] Nilsson A, Isgaard J, Lindahl A. et al. Regulation by growth hormone of number of chondrocytes containing IGF-I in rat growth plate[J]. Science. 1986.233:571-574.
[46] Green H, Morikawa M, Nixon T. et al. A dual effector theory of growth-hormone action[J]. Differentiation. 1985.29:195-198.
[47] Hiragun A, Sato M, Mitsui H. et al. Establishment of a clonal cell line that differentiates into adipose cells in vitro[J]. In Vitro 1980,16:685- 693.
[48] Rubin CS, Hirsch A, Fung C. et al. Development of hormone receptors and hormonal responsiveness in vitro. Insulin receptors and insulin sensitivity in the preadipocyte and adipocyte forms of 3T3-L1 cells[J]. J Biol Chem. 1978. 253:7570-7578.
[49] Nixon T, Green H. Properties of growth hormone receptors in relation to the adipose conversion of 3T3 cells[J]. J Cell Physiol. 1983.115:291-296.
[50] Morikawa M, Green H, Lewis UJ. Activity of human growth hormone and related polypeptides on the adipose conversion of 3T3 cells[J]. Mol Cell Biol. 1984. 4:228-231.
[51] Wang J,Zhou J,Bondy CA. IGF-I promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy[J].FASEB J.1999.13:1985-1990.
[52] Lupu F, Kaechoong L, Segro GV, et al. Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth[J]. Dev Biol. 2001.229:141-162.
[53] S.A.Kaplan, P.Cohen. REVIEW: The Somatomedin Hypothesis 2007: 50 Years Later[J]. The Journal of Clinical Endocrinology & Metabolism. 2007.92(12):4529-4535.
[54] Guevara-Aguirre J RA, Vasconez O, Martinez V. et al. Two year treatment of growth hormone (GH)receptor deficiency with recombinant insulin-like growth factor-1 in 22 children: comparison of two dosage levels and to GH-treatedGHdeficiency[J]. J Clin Endocrinol Metab. 1997.82:629-633.
[55] Ranke MB, Chatelain PG, Preece MA. et al. Long-term treatment of growth hormone insensitivity syndrome with IGF-I. Results of the European Multicentre Study. The Working Group on Growth Hormone Insensitivity Syndromes[J]. Horm Res. 1999. 51:128-134.
[56] LeRoith D, Yakar S, Liu JL. et al. The Somatomedin Hypothesis 2001 [J]. Endocrine Reviews. 2001.22(1):53-74.
[57] Daughaday W H, Hall K, Raben M S. et al. Somatomedin: a proposed designation for the sulfation factor[J]. Nature. 1972.235:107.
[58] Froesch ER, Burgi H, Ramseier EB, et al. Antibodysuppressible and nonsuppressible insulin-like activities in human serum and their physiologic significance. An insulin assay with adipose tissue of increased precision and specificity[J]. J Clin Invest 1963.42:1816-1834.
[59] Rinderknecht E, Humbel RE. Polypeptides with nonsuppressible insulin-like and cell-growth promoting activities in human serum: isolation, chemical characterization,and some biological properties of forms I and II[J]. Proc Natl Acad Sci USA. 1976. 73:2365-2369.
[60] Rotwein P. Structure, evolution, expression and regulation of insulin-like growth factors I and II[J].Growth Factors. 1991. 5:3-18.
[61] Sandra D. O'Dell,Ian N. M. Day. Molecules in focus Insulin-like growth factor II (IGF-II) [J]. The International Journal of Biochemistry & Cell Biology. 1998. 30(7):767-771.
[62] W.Engstr(?)m,A. Shokrai,K.Otte. et al. Transcriptional regulation and biological significance of the insulin like growth factor II gene[J]. Cell Proliferation. 1998. 31(5): 173-189.
[63] Shili Zhan, Lijuan Zhang, Marcus Van, et al. Biallelic expression of all four IGF-II promoters and its association with increased methylation of H19 gene in human brain Brain Research[J]. 1998.792(2):283-290
[64] AV Lallemand, PM Joly, DA Gaillard, et al. In vivo localization of the insulin-like growth factors I and II (IGF I and IGF II) gene expression during human lung development[J]. Int J Dev Biol. 1995.39(3):529-537.
[65] Lopez MF, Dikkes, P,Zurakowski, et al. Regulation of hepatic glycogen in the insulin-like growth factor II-deficient mouse[J]. Endocrinology. 1999. 140(3):1442-1448.
[66] K Malhotra, LL Costello, TJ Raich, et al. Identification of differentially expressed mRNAs in human fetal liver across gestation[J]. Nucleic Acids Research. 1999. 27(3):839-847.
[67] Birnbacher Robert AG, Breitschopf Helene,Lassmann Hans. Et al. Cellular Localization of Insulin-Like Growth Factor II mRNA in the Human Fetus and the Placenta: Detection with a Digoxigenin-Labeled cRNA Probe and Immunocytochemistry[J]. Pediatric Research. 1998.43(5):614-620.
[68] Verhaeghe, Johan, Van Bree. et al. C-Peptide, Insulin-Like Growth Factors I and II, and Insulin-Like Growth Factor Binding Protein-1 in Umbilical Cord Serum: Correlations With Birth Weight[J]. American Journal of Obstetrics and Gynecology. 1993. 169(1):89-97.
[69] S Halvorsen,AG Bechensteen, Physiology of erythropoietin during mammalian development[J].Acta Paediatrica. 2002. 91(438): 17 - 26.
[70] T. Mushtaq, S. F. Ahmed, C. Farquharson. et al. Insulin-Like Growth Factor-I Augments Chondrocyte Hypertrophy and Reverses Glucocorticoid-Mediated Growth Retardation in Fetal Mice Metatarsal Cultures[J]. Endocrinology. 2004. 145(5):2478-2486.
[71] Vander EB, Karperien M. Systemic and regulation of the growth plate[J]. Endocr Rev. 2003.24(6):782-801.
[72] Wang J,Zhou J,Bondy CA. et al. IGF-I promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy[J]. The FASEB Journal. 1999.13(14):1985-1990.
[73] Andrea Giustina GM, Ernesto Canalis. Growth Hormone, Insulin-Like Growth Factors, and the Skeleton[J]. Endocrine Reviews. 2008. 29(5):535-559.
[74] Michele R. Hutchison M, Perrin C. et al. Insulin-Like Growth Factor-I and Fibroblast Growth Factor, But Not Growth Hormone, Affect Growth Plate Chondrocyte Proliferation[J].Endocrinology. 2007. 148(7):3122-3130.
[75] Floria Lupua, Kaechoong Leec,Gino V. et al. Roles of Growth Hormone and Insulin-like Growth Factor 1 in Mouse Postnatal Growth[J]. Developmental Biology. 2001. 229:141-162.
[76] S.Mohan, R. Guo, Y. Amaar, et al. Insulin-Like Growth Factor Regulates Peak Bone Mineral Density in Mice by Both Growth Hormone-Dependent and -Independent Mechanisms[J].Endocrinology. 2003.144(3):929 - 936.
[77] Yuan Song YU, Zheng Bin HAN,Wei LI, et al. Apoptosis in Granulosa cells during follicular atresia: relationship with steroids and insulin-like growth factors[J]. Cell Research. 2004.14:341-346.
[78] Nuttinck F, Mermillod P, Loosfelt H, et a. Expression of components of the insulinlike growth factor system and gonadotropin receptors in bovine cumulus-oocyte complexes during oocyte maturation[J]. Domestic Animal Endocrinology. 2004.27:179-195.
[79] Sudo N, Kawashima C, Kaneko E, et al. Insulin-like growth factor-I (IGF-I) system during follicle development in the bovine ovary: relationship among IGF-I, type 1 IGF receptor (IGFR-1) and pregnancy-associated plasma protein-A (PAPP-A) [J]. Molecular and Cellular Endocrinology. 2007.264:197-203.
[80] Wasielak M. Apoptosis inhibition by insulin-like growth factor (IGF)-I during in vitro maturation of bovine oocytes[J]. Journal of Reproduction and Development 2007. 53:419-426.
[81] H C Liu, Y X Tang, C A Mele, et al. Simultaneous detection of multiple gene expression in mouse and human individual preimplantation embryos[J]. Fertil Steril. 1997. 674:733-741.
[82] Austin EJ, Evans ACO, Knight PG et al. Alterations in intrafollicular regulatory factors and apoptosis during selection of follicles in the first follicular wave of the bovine estrous cycle[J].Biology of Reproduction. 2001. 64:839-848.
[83] Nicholas B, Armstrong DG, Webb R, et al. Changes in insulin-like growth factor binding protein (IGFBP) isoforms during bovine follicular development[J]. Reproductioa 2002. 124:439-446.
[84] Shabrine S. Daftary.Andrea C. Gore, et al. IGF-1 in the Brain as a Regulator of Reproductive Neuroendocrine Function[J]. Experimental Biology and Medicine. 2005. 230:292-306.
[85] JK Hiney, CL Nyberg, SR Ojeda. et al. Insulin-like growth factor I of peripheral origin acts centrally to accelerate the initiation of female puberty[J]. Endocrinology. 1996. 137:3717-3728.
[86] Wison M. E. Premature elevation in serum insulin-like growth faetor-I advances forst ovulation in rhesus monkeys[J]. Journal of Endocrinology. 1998.158:247-257.
[87] CL Adam, PA Findlay, DC Wathes. et al. IGF-I stimulation of luteinizing hormone secretion,IGF-binding proteins (IGFBPs) and expression of mRNAs for IGFs, IGF receptors and IGFBPs in the ovine pituitary gland[J]. Journal of Endocrinology. 2000.166:247-254
[88] M D Ashworth, D R Stein, D T Allen, et al. Endocrine disruption of uterine insulin-like growth factor expression in the pregnant gilt. Reproduction[J]. 2005. 130:545-551.
[89] Cerro, J. A.Pintar, J. E. Insulin-like growth factor binding protein gene expression in the pregnant rat uterus and placenta[J]. Dev Biol. 1997.184(2):278-295.
[90] N.R Nayaka,L.C Giudice. Comparative Biology of the IGF System in Endometrium, Decidua, and Placenta, and Clinical Implications for Foetal Growth and Implantation Disorders[J]. Placenta.2003.24(4):281-296
[91] Dehnhard MC, R.Munz, O.Weiler, et al. Course of epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) in mammary secretions of the goat during end-pregnancy and early lactation[J]. J Vet Med A Physiol Pathol Clin Med 2000. 47(9):533-540.
[92] D.J.Flinta, E. Tonnera,C.J. Wildea, et al. Insulin-like growth factor binding proteins initiate cell death and extracellular matrix remodeling in the mammary gland[J]. Domestic Animal Endocrinology. 2005.29(2):274-282
[93] Lewitt M S, Saunders H, Phuyal J L, et al. Complex formation by human insulin-like growth factor-binding protein-3 and human acid-labile subunit in growth hormone-deficient rats[J].Endocrinology. 1994.134:2402-2409.
[94] Kanety H, Karasik A, Klinger B, et al. Long-term treatment of Laron type dwarfs with insulin-like growth factor I increases serum insulin-like growth factor-binding protein 3 in the absence of growth hormone activity[J].Acta Endocrinol. 1993. 128:144-159.
[95] Leal SM, Huang SS, Huang JS. et al. Interactions of high affinity insulin-like growth factor-binding proteins with the type V transforming growth factor-b receptor in mink lung epithelial cells[J]. J Biol Chem. 1999.274:6711-6717.
[96] Reinecke M, Collet C. The phylogeny of the insulin-like growth factors[J]. Int Rev Cytol. 1998. 183:1-94.
[97]Vivian Hwa,Youngman Oh,Ron G.Rosenfeld.The Insulin-Like Growth Factor-Binding Protein (IGFBP) Superfamily[J].Endocrine Reviews.1999.20(6):761-787.
[98]Neumann G,Bach L.The N-terminal disulfide linkages of human insulin-like growth factor-binding protein-6(hIGFBP-6) and hIGFBP-1 are different as determined by mass spectrometry[J].J Biol Chem.1999.274:14587-14594.
[99]Hashimoto R,Fujiwara H,Higashihashi N,et al.Binding sites and binding properties of binary and ternary complexes of insulin-like growth factor-Ⅱ(IGF-Ⅱ),IGF-binding protein-3,and acid-labile subunit[J].J Biol Chem.1997.272:27936-27942.
[100]Zapf J,Chang JY,James P,et al.Isolation and NH2-terminal amino acid sequences of rat serum carrier proteins for insulin-like growth factors[J].Biochem Biophys Res Commun.1988.156:1187-1194.
[101]Ceda G P,Henzel W J,Louie A,et al.Differential effects of insulin-like growth factor(IGF)-Ⅰ and IGF-Ⅱ on the expression of IGF binding proteins(IGFBPs) in a rat neuroblastoma cell line:isolation and characterization of two forms of IGFBP-4[J].Endocrinology.1991.128:2815-2824.
[102]Claussen M,Schuller AG,Matzner U,et al.Regulation of insulin-like growth factor(IGF)-binding protein-6 and mannose 6-phosphate/IGF-Ⅱ receptor expression in IGF-IL-overexpressing NIH 3T3cells[J].Mol Endocrinol.1995.9:902-912.
[103]Westwood M,White A.Purification and characterization of the insulin-like growth factor-binding protein-1 phosphoform found in normal plasma[J].Endocrinology.1997.138:1130-1136.
[104]Jones JI,Wright G,Smith CE,et al.Identification of the sites of phosphorylation in sinulin-like growth factor binding protein-1:regulation of its affinity by phosphorylation of serinel01[J].J Biol Chem.1993.268:1125-1131.
[105]Coverley JA.Regulation of insulin-like growth factor(IGF) binding protein-3 phosphorylation by IGF-Ⅰ[J].Endocrinology.1995.136:5778-5781.
[106]Thompson JD,Gibson TJ.CLUSTAL W:improving the sensitivity of progressive multiple sequence alignment through sequence weighting,position-specific gap penalties and weight matrix choice[J].Nucleic Acids Research.1994.22(4673-4680).
[107]Forbes B E,Hodge S J,McNeil K A,et al.Localization of an insulin-like growth factor(IGF)binding site of bovine IGF binding protein-2 using disulfide mapping and deletion mutation analysis of the C-terminal domain[J].J Biol Chem.1998.273:4647-4652.
[108]Malthiery Y,Lissitzky S.Primary structure of human thyroglobulin deduced from the sequence of its 8448-base complementary DNA[J].Eur J Biochem.1987.165:491-498..
[109]Sala AC,S.Campagnoli,M.Faggion,et al.Structure and properties of the C-terminal domain of insulin-like growth factor-binding protein-1 isolated from human amniotic fluid[J].J Biol Chem.2005.280(33):29812-29819.
[110]Fowlkes JL,George-Nascimento C,Rosenberg CK,et al.Heparin-binding,highly basic regions within the thyroglobulin type-Ⅰ repeat of insulin-like growth factor(IGF)-binding protleins (IGFBPs) -3,-5,and -6 inhibit IGFBP-4 degradation.Endocrinology[J].1997.138:2280-2285.
[111]Kuang ZY,S.McNeil,K.A.Thompson,et al.Cooperativity of the N- and C-terminal domains of insulin-like growth factor(IGF) binding protein 2 in IGF binding[J].Biochemistry.2007.46(48):13720-13732.
[112]Zhihe Kuang,David W.Keizer,Chunxiao C.et al.Structure,Dynamics and Heparin Binding of the C-terminal Domain of Insulin-like Growth Factor-binding Protein-2(IGFBP-2)[J].Journal of Molecular Biology. 2006. 364(4):690-704
[113]R. Rajah, B. Valentinis, P. Cohen, et al. Insulin-like growth factorbinding proteins in serum and other biological fluids: regulation and functions[J]. Endocr Rev. 1997.18:801-831.
[114]Qin X, Baylink DJ, Mohan S. et al. Structure-function analysis of the human insulin-like growth factor binding protein-4[J]. J Biol Chem. 1998. 273:23509-23516.
[115]Imai Y, Smith CE, Clarke JB, et al. Protease-resistant form of insulin-like growth factor-binding protein 5 is an inhibitor of insulinlike growth factor-I actions on porcine smooth muscle cells in culture[J]. J Clin Invest 1997. 100:2596-2605.
[116]Bramani S, Beattie J, Tonner E, et al. Amino acids within the extracellular matrix (ECM) binding region (201-218) of rat insulin-like growth factor binding protein (IGFBP-5) are important determinants in binding IGF-I. J Mol Endocrinol. 1999.23:117-123.
[117]Iosef CG, T.Jia, C. Y.Li, et al. A functional nuclear localization signal in insulin-like growth factor binding protein-6 mediates its nuclear import[J]. Endocrinology. 2008. 149(3): 1214-1226.
[118]Oh Y MH, Lamson G, Rosenfeld RG. Insulin-like growth factor (IGF)-independent action of IGF-binding protein-3 in Hs578T human breast cancer cells. J Biol Chem. 1993.268:14964-14971.
[119]Fu, P.Thompson, J. A.Bach, L. A. Promotion of cancer cell migration: an insulin-like growth factor (IGF)-independent action of IGF-binding protein-6[J]. J Biol Chem. 2007. 282(31):22298-22306.
[120]Kalus W, Renner C, SanchezY, et al. Structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions[J].EMBO J. 1998. 17:6558-6572.
[121]Sara V, Andersson C, Hall E, et al. Characterization of somatomedins from human fetal brain:identification of a variant form of insulin-like growth factor I[J]. Proc Natl Acad Sci USA. 1986.83:4904-4907.
[122]Forbes B, Baxter RC, Ballard FJ, et al. Classification of the insulin-like growth factor binding proteins into three distinct categories according to their binding specificities[J]. Biochem Biophys Res Commua 1988.157:196-202.
[123]Clemmons DR, Camacho-Hu bner C, Mc-Cusker RH, et al. Discrete alterations of the insulin-like growth factor I molecule which alter its affinity for insulin-like growth factor-binding proteins result in changes in bioactivity[J]. J Biol Chem. 1990.265:12210-12216.
[124]Bach LA, Sakano K, Fujiwara H, et al. Binding of mutants of human insulin-like growth factor II to insulin-like growth factor binding proteins 1-6[J]. J Biol Chem. 1993.268:9246-9254.
[125]Baxter RC. Insulin-like growth factor (IGF)-binding proteins:interactions with IGFs and intrinsic bioactivities[J]. Am J Physiol Endocrinol Metab. 2000. 278:967-976.
[126]Vorwerk P, Spagnoli A, Oh Y, et al. Insulin and IGF binding by IGFBP-3 fragments derived from proteolysis, baculovirus expression and normal human urine[J]. J Clin Endocrinol Metab. 1998.83:1392-1395.
[127]Hobba GD, Holmberg E, Forbes BE, et al. Alanine screening mutagenesis establishes tyrosine 60 of bovine insulin-like growth factor binding protein-2 as a determinant of insulin-like growth factor binding[J]. J Biol Chem. 1998. 273:19691-19698.
[128]Qin X, Baylink D J, Mohan S. Structurefunction analysis of the human insulin-like growth factor binding protein-4. J Biol Chem. 1998. 273:23509-23516.
[129]Imai Y, Clarke J B, Busby W, et al. Synthesis and characterization of IGFBP-5 and IGFBP-3 mutants that have no affinity for IGF-I[J]. GH and IGF Res. 1999. 9:372.
[130]Firth S M, Baxter R C. Structural determinants of ligand and cell-surface binding of insulin-like growth factor-binding protein-3[J]. J Biol Chera 1998. 273:2631-2638.
[131]Jones J I, Camacho H C, Clemmons D R, et al. Phosphorylation of insulin-like growth factor (IGF)-binding protein 1 in cell culture and in vivo: effects on affinity for IGF-I[J]. Proc Natl Acad Sci USA. 1991.88:7481-7485.
[132]Frystyk J, Skj(?)rbask C, (?)rskov H. The effect of oral glucose on serum free insulin-like growth factor-I and -II in healthy adults[J]. J Clin Endocrinol Metab. 1997. 82:3124-3127.
[133]Ho P J,Baxter R C. Characterization of truncated insulinlike growth factor-binding protein-2 in human milk[J]. Endocrinology. 1997. 138:3811-3818.
[134]Lalou C, Lassarre C, Binoux M. A. et al. proteolytic fragment of insulin-like growth factor (IGF) binding protein-3 that fails to bind IGFs inhibits the mitogenic effects of IGF-I and insulin[J].Endocrinology. 1996. 137:3206-3212.
[135]Lassarre C,Binoux M. et al. Insulin-like growth factor binding protein-3 is functionally altered in pregnancy plasma[J]. Endocrinology. 1994. 134:1254-1262.
[136]Baxter R C.Skriver L. Altered ligand specificity of proteolysed insulin-like growth factor binding protein-3[J]. Biochem Biophys Res Commun. 1993.196:1267-1273.
[137]J.I. Jones, W.H. Busby, G Wright, et al. Insulin-like growth factor binding protein1 stimulates cell migration and binds to the a5bl integrin by means of its Arg-Gly-Asp sequence[J]. Proc Natl Acad Sci USA. 1993. 90. 10553-10557.
[138]L.M. Gleeson, C. Chakraborty, T. McKinnon. et al. Insulinlike growth factor-binding protein1 stimulates human trophoblast migration by signaling through alpha 5 beta1 integrin via mitogenactivated protein Kinase pathway[J]. J Clin Endocrinol Metab. 2001, 86 2484-2493.
[139]C.M. Perks, P.V. Newcomb, M.R. Norman, et al. Effect of insulin-like growth factor binding protein-1 on integrin signaling and the induction of apoptosis in human breast cancer cells[J]. J Mol Endocrinol. 1999.22:141-150.
[140]J.M. Ricort, M. Binoux. Insulin-like growth factor binding protein (IGFBP) signalling[J]. Growth Hormone & IGF Research. 2004. 14 277-286.
[141]J.I. Leu, M.A. Crissey, R. Taub. Massive hepatic apoptosis associated with TGF-beta 1 activation after Fas ligand treatment of IGF binding protein-1-deficient mice[J]. J Clin Invest 2003.111:129-139.
[142]Shahjee HB, N.Zappala, GWiench, et al. An N-terminal fragment of insulin-like growth factor binding protein-3 (IGFBP-3) induces apoptosis in human prostate cancer cells in an IGF-independent manner[J]. Growth Horm IGF Res. 2008. 18 (3 ):188-197.
[143]L.Buckbinder, S. Velasco-Miguel, I. Takenaka, et al. Induction of the growth inhibitor IGF-binding protein 3 by p53[J]. Nature. 1995. 377:644-649.
[144]T. Nickerson, H. Huynh, M. Pollak. Insulin-like growth factor binding protein-3 induces apoptosis in MCF7 breast cancer cells[J]. Biochem Biophys Res Commua 1997. 237:690-693.
[145]C.M.Perks, Z.P.Gill, P.V.Newcomb, et al. Differential IGF-independent effects of insulin-like growth factor binding proteins (1-6) on apoptosis of breast epithelial cells[J]. JCell Biochem. 1999.75:652-664.
[146]A. Butt, M. King, R. Baxter, et al. Insulin-like growth factorbinding protein-3 modulates expression of Bax and Bcl-2 and potentiates p53-independent radiation-induced apoptosis in human breast cancer cells[J]. J Biol Chem. 2000, 275:39174-39181.
[147]A.C. Williams, CM. Perks, P. Newcomb, et al. Increased p53-dependent apoptosis by the insulin-like growth factor binding protein IGFBP-3 in human colonic adenoma-derived cells[J].Cancer Res. 2000.60:22-27.
[148]R. Rajah, B. Valentinis, P. Cohen. Insulin-like growth factorbinding protein-3 induces apoptosis and mediates the effects of transforming growth factor-b1 on programmed cell death through a p53-and IGF-independent mechanism[J]. J Biol Chem. 1997.272:12181-12188.
[149]A. Spagnoli, S.R. Nagalla, W.A. Horton, et al. Identification of STAT-1 as a molecular target of IGFBP-3 in the process of chondrogenesis[J]. J Biol Chem. 2002. 277:18860-18867.
[150]S.E. Damon, J.L. Ware, S.R. Plymate. et al. Overexpression of an inhibitory insulin-like growth factor binding protein (IGFBP), IGFBP-4, delays onset of prostate tumor formation[J].Endocrinology 1998. 139:3456-3464.
[151JR.H. Drivdahl, K. Trimm, S.R. Plymate, et al. Inhibition of growth and increased expression of insulin-like growth factorbinding protein-3 (IGFBP-3) and -6 in prostate cancer cells stably transfected with antisense IGFBP-4 complementary deoxyribonucleic acid[J]. Endocrinology 2001.142:1990-1998.
[152]A.J. Butt, F. McDougall, R.C. Baxter, et al. Insulin-like growth factor-binding protein-5 inhibits the growth of human breast cancer cells in vitro and in vivo[J].J Biol Chem.2003.278:29676-29685.
[153]B. Liu, S. Weinzimer, D. Powell, et al. Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-alpha regulate transcriptional signaling and apoptosis[J]. J Biol Chem. 2000. 275:33607-33613.
[154]Y.G Amaar, T.A. Linkhart, S.T. Chen, et al. Insulin-like growth factor-binding protein5 (IGFBP-5) interacts with a four and a half LIM protein 2 (FHL2) [J]. J Biol Chem. 2002.277:12053-12060.
[155]L.J. Schedlich, G.M. Leong, R.C. Baxter, et al. Insulin like growth factor binding protein-3 prevents retinoid receptor heterodimerization: implications for retinoic acid-sensitivity in human breast cancer cells[J]. Biochem Biophys Res Commua 2004. 314:83-88.
[156]S. Fanayan, A.J. Butt, R.C. Baxter, et al. Growth inhibition by insulin-like growth factor-binding protein-3 in T47D breast cancer cells requires transforming growth factor-beta (TGF-beta) and the type II TGF-beta receptor[J]. J Biol Chem. 2000. 275:39146-39151.
[15]S. Fanayan, S.M. Firth, R.C. Baxter. Signaling through the Smad pathway by insulin-like growth factor-binding protein-3 in breast cancer cells. Relationship to transforming growth factor-beta 1 signaling[J]. J Biol Chem. 2002. 277:7255-7261.
[158]R. Oklu, R. Hesketh. The latent transforming growth factor beta binding protein (LTBP) family[J].Biochem J. 2000. 352 (Pt 3):601-610.
[159]Y. Gui, L.J. Murphy. Interaction of insulin-like growth factor binding protein-3 with latent transforming growth factor-beta binding protein-1[J]. Mol Cell Biochem. 2003. 250:189-195.
[160]J.L. Martin, R.C. Baxter. Oncogenic ras causes resistance to the growth inhibitor insulin-like growth factor binding protein-3 (IGFBP-3) in breast cancer cells[J]. J Biol Chem. 1999.274:16407-16411.
[161]J.L. Martin, S.M. Weenink, R.C. Baxter. Insulin-like growth factor-binding protein-3 potentiates epidermal growth factor action in MCF-10A mammary epithelial cells. Involvement of p44/42 and p38 mitogen-activated protein kinases[J]. J Biol Chem. 2003. 278 2969-2976.
[162]C.A. Conover, S.K. Durham, D.R. Powell, et al. Insulin-like growth factor (IGF) binding protein-3 potentiation of IGF action is mediated through the phosphatidylinositol-3-kinase pathway and is associated with alteration in protein kinase B/AKT sensitivity[J]. Endocrinology. 2000. 141:3098-3103.
[163]J.M. Ricort, M. Binoux. Insulin-like growth factor binding protein-3 stimulates phosphatidylinositol 3-kinase in MCF-7 breast carcinoma cells[J]. Biochem Biophys Res Commun.2004.314 1044-1049.
[164]J.M. Ricort, M. Binoux. Insulin-like growth factor-binding protein-3 activates a phosphotyrosine phosphatase. Effects on the insulin-like growth factor signaling pathway[J]. J Biol Chem. 2002.277:19448-19454.
[165]J.M. Ricort, M. Binoux. Insulin-like growth factor binding protein-3 inhibits type 1 insulin-like growth factor receptor activation independently of its insulin-like growth factor binding affinity[J].Endocrinology. 2001. 142 108-113.
[166]Kato H, Faria TN, Stannard B, et al. Essential role of tyrosine residues 1131, 1135,and 1136 of the insulin-like growth factor-I (IGF-I) receptor in IGF-I action. Mol Endocrinology. 1994. 8:40-50.
[167]LeRoith D, Werner H, Beitner-Johnson D, et al. Molecular and cellular aspects of the insulin-like growth factor I receptor[J]. Endocr Rev. 1995. 16:143-163.
[168]Y Yang, J Niu,L Guo. The effects of antisense insulin-like growth factor-I receptor oligonucleotide on human cord blood lymphocytes. Journal of Molecular[J] Endocrinology. 2002. 28(3):207-212.
[169]Bondy CA,Werner H, Roberts CT, Jr, et al. Cellular pattern of insulin-like growth factor I (IGF-I) and type I IGF receptor gene expression in early organogenesis: comparison with IGF-II gene expression[J]. Mol Endocrinol. 1990.4:1386-1398.
[170]kornfeld s. Structure and function of the mannose 6-phosphate/insulinlike growth factor II receptors[J]. Annu Rev Biochem. 1992., 61:307-330.
[171]M J Ellis,BA Leav,Z Yang,et al. Affinity for the insulin-like growth factor-II (IGF-II) receptor inhibits autocrine IGF-II activity in MCF-7 breast cancer cells[J]. Molecular Endocrinology. 1996.10:286-297.
[172]Zhihong Chen,Yinlin Ge,Jing X Kang. Down-regulation of the M6P/IGF-II receptor increases cell proliferation and reduces apoptosis in neonatal rat cardiac myocytes[J]. BMC Cell Biology. 2004.5(15):1-12.
[173]Jawon Seo,Kong-Joo Lee. Post-translational Modifications and Their Biological Functions:Proteomic Analysis and Systematic Approaches[J]. Journal of Biochemistry and Molecular Biology.2004. 37(1):35-44.
[174]Ficarro S B, McCleland M L, Stukenberg P T. Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nature Biotechnology. 2002.20(3):301-305.
[175]Krupa A, Preethi G, Srinivasan N. Structural modes of stabilization of permissive phosphorylation sites in protein kinases:distinct strategies in Ser/Thr and Tyr kinases[J]. J Mol Biol. 2004.339:1025-1039.
[176]Fowler D, Albaiges, G, Lees, C, Jones, J.,et al. The role of insulin-like growth factor binding protein-1 phosphoisoforms in pregnancies with impaired placental function identified by doppler ultrasound[J]. Hum Reprod. 1999. 14:2881-2885.
[177]Yu J, Iwashita, M., Kudo, Y.,et al. Phosphorylated insulin-like growth factor(IGF)-binding protein-1 (IGFBP-1) inhibits while non-phosphorylated IGFBP-1 stimulates IGF-Iinducedamino acid uptake by cultured trophoblast cells[J]. Growth Horm IGF Res. 1998. 8:65-70.
[178]Gibson JM, Aplin J. D., White, A., et al. Regulation of IGF bioavailability in pregnancy[J]. Mol Hum Reprod. 2001. 7:79-87.
[179]Nissum MA, M.Sukop, U.Khosravi, et al. Functional and complementary phosphorylation state attributes of human insulin-like growth factor binding protein-1( IGFBP-1) isoforms resolved by free flow electrophoresis[J]. Mol Cell Proteomics. 2009.
[180]Seferovic M, R.Kamei, H.Liu, et al. Hypoxia and leucine deprivation induce human insulin-like growth factor binding protein-1 hyperphosphorylation and increase its biological activity[J].Endocrinology. 2009. 150(1):220-231.
[181]Graham M, D. M.Firth, S. M.Robinson, et al. The in vivo phosphorylation and glycosylation of human insulin-like growth factor-binding protein-5[J]. Mol Cell Proteomics. 2007. 6120(8):1392-1405.
[182]Schedlich L, T.John, A. P.Jans, et al. Phosphorylation of insulin-like growth factor binding protein-3 by deoxyribonucleic acid-dependent protein kinase reduces ligand binding and enhances nuclear accumulation[J]. Endocrinology. 2003. 144(5): 1984-1993.
[183]Blom N, Sicheritz-Ponten T, Gupta R. Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence[J]. Proteomics. 2004.4:1633-1649.
[184]Gavel Y, von Heijne G. Statistical studies of N-glycosylated proteins have indicated that the frequency of nonglycosylated Asn-Xaa-(Thr/Ser) sequons increases toward the C terminus[J].Protein Eng. 1990,3:433-442.
[185]Marinaro J, G. M.Russo, V. C.Leeding, K. S. et al. O-glycosylation of insulin-like growth factor (IGF) binding protein-6 maintains high IGF-II binding affinity by decreasing binding to glycosaminoglycans and susceptibility to proteolysis[J]. Eur J Biochem. 2000.267(17):5378-5386.
[186]Firth, S. M.Baxter, R. C. Characterisation of recombinant glycosylation variants of insulin-like growth factor binding protein-3[J]. J Endocrinol. 1999.160(3):379-387.
[187]Igor Siwanowicz, Magdalena Wisniewska. Structural Basis for the Regulation of Insulin-like Growth Factors by IGF Binding Proteins[J]. Structure. 2005.13:155-167.
[188]Payet LD, Wang, X.H., Baxter, R.C., et al. Amino and carboxyl-terminal fragments of insulin-like growth factor (IGF)binding protein-3 cooperate to bind IGFs with high affinity and inhibit IGF receptor interactions[J]. Endocrinology. 2003. 144: 2797-2806.
[189]Shand JH, Beattie, J., Song, H., et al. Specific amino acid substitutions determine the differential contribution of the N- and C-terminal domains of insulin-like growth factor (IGF)-binding protein-5 in binding IGF-I[J]. J Biol Chem. 2003.278(17859-17866).
[190]Buckway CK, Wilson, E.M., Ahlsen, M.,et al. Mutation of three critical amino acids of the N-terminal domain of IGF-binding protein-3 essential for high affinity IGF binding[J]. J Clin Endocrinol Metab. 2001. 86:4943-4950.
[191]Buel D. Rodgers, Cullen Thompson. Phylogenetic analysis of the insulin-like growth factor binding protein (IGFBP) and IGFBP-related protein gene families[J]. General and Comparative Endocrinology. 2008. 155:201-207.
[192]Jones JL, Doerr ME. Cell migration: interactions among integrins, IGFs and IGFBPs[J]. Prog Growth Factor Res. 1995. 6:319-327.
[193]Vandesompele J, De Preter K, Pattyn F, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes[J]. Genome Biol. 2002.3(7):34-42.
[194]Lee RS, Depree KM, Davey HW. The sheep (Ovis aries) H19 gene:genomic structure and expression patterns, from the preimplantation embryo to adulthood[J]. Gene. 2002. 301:67-77.
[195]Todorovic VP, P.Micev, M.Bjelovic, et al. Insulin-like growth factor-I in wound healing of rat skin[J]. Regul Pept 2008. 150(1-3):7-13.
[196]Joseph D'Ercole, A.Ye, P. Expanding the mind: insulin-like growth factor I and brain development[J]. Endocrinology. 2008.149(12):5958-5962.
[197]Ruo L. Chen NAK, Mahvand Sadeghi, et al. Insulin-Like Growth Factor-II Uptake Into Choroid Plexus and Brain of Young and Old Sheep[J]. Journal of Gerontology. 2008. 63(2): 141-148.
[198]Chowen J, L.Ramos, S.Busiguina, et al. Effects of early undernutrition on the brain insulin-like growth factor-I system[J]. J Neuroendocrinol. 2002.14(2):163-169.
[199]Cheng C, R. R.Lee, W. H.Joncas, et al. Insulin-like growth factor 1 regulates developing brain glucose metabolism[J]. ProcNatl Acad Sci U S A. 2000.97(18):10236-10241.
[200]Werther G, V.Baker, N.Butler, et al. The role of the insulin-like growth factor system in the developing brain[J]. Horm Res. 1998.49 (Suppl 1):37-40.
[201]Ye, P.D'Ercole, J. Insulin-like growth factor I (IGF-I) regulates IGF binding protein-5 gene expression in the brain[J]. Endocrinology. 1998. 139(1):65-71.
[202]Yasuoka HL, A. T.Yamaguchi, Y.Feghali-Bostwick, et al. Human skin culture as an ex vivo model for assessing the fibrotic effects of insulin-like growth factor binding proteins[J]. Open Rheumatol J.2008.2:17-22.
[203]Reijnders C, N.HoIzmann, P. J.Bhoelan, et al. In vivo mechanical loading modulates insulin-like growth factor binding protein-2 gene expression in rat osteocytes[J]. Calcif Tissue Int 2007.80(2):137-143.
[204.]R. L.Mamabolo, N. S.Levitt, H. A.Delemarre-van de Waal, et al. Association between insulin-like growth factor-1, insulin-like growth factor-binding protein-1 and leptin levels with nutritional status in 1-3-year-old children, residing in the central region of Limpopo Province, South Africa[J].Br J Nutr. 2007. 98(4):762-769.
[205]Lelbach, A.Scharf, J. G.Ramadori, G. Regulation of insulin-like growth factor-I and of insulin-like growth factor binding protein-1, -3 and -4 in cocultures of rat hepatocytes and Kupffer cells by interleukin-6[J]. J Hepatol. 2001. 35(5):558-567.
[206]Kamangar, B. B.Gabillard, J. C.Bobe, J. Insulin-like growth factor-binding protein (IGFBP)-1, -2,-3, -4, -5, and -6 and IGFBP-related protein 1 during rainbow trout postvitellogenesis and oocyte maturation: molecular characterization, expression profiles, and hormonal regulation[J].Endocrinology. 2006. 147(5):2399-2410.
[207]Stephens M, Smith N, Donnelly P. A new statistical method for haplotype reconstruction from population data. American Journal of Human[J] Genetics. 2001. 68:978-989.
[208]T Noumi, S Natori,M Futai, et al. A phenylalanine for serine substitution in the beta subunit of Escherichia coli F1-ATPase affects dependence of its activity on divalent cations[J]. J Biol Chem.1984. 259(16): 10071-10075.
[209]M Orita HI, H Kanazawa,K Hayashi, et al. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms[J]. Proc Natd Acad Sci USA. 1989.86 (8):2766-2770.
[210]Orita M, Sekiya T,Hayashi K. et al. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction[J]. Genomics. 1989.5(4):874-879.
[211]Hoshino S, Fukuda Y,Dohi K,Sasazuki T, et al. Polymerase chain reaction-single-strand conformation polymorphism analysis of polymorphism in DPA1 and DPB1 genes: a simple,economical, and rapid method for histocompatibility testing[J].Hum Immunol. 1992. 33(2):98-107.
[212]Spinardi L, Mazars R, Theillet C. Protocols for an improved detection of point mutation by SSCP[J]. Nucleic Acids Research. 1991. 19(14):4009.
[213]Fu YH, Pizzuti A, Pieretti M, et al. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox[J]. Cell. 1992.67(6): 1047-1058.
[214]Botstein D, Skolnick M, Davis RW, et al. Construction of a genetic linkage map in man using restriction fragment length polymorphism[J]. American Journal of Human Genet 1980.32(3):314-331.
[215]B Dalrymple, E Kirkness, M Nefedov, et al. Using comparative genomics to reorder the human genome sequence into a virtual sheep genome[J].Genome Biology. 2007. 8(7):R152.152-R152.120.
[216]Bennett, A. K.Hester, P. Y.Spurlock, D. E. Polymorphisms in vitamin D receptor, osteopontin,insulin-like growth factor 1 and insulin, and their associations with bone, egg and growth traits in a layer-broiler cross in chickens[J]. Anim Genet 2006. 37(3):283-286.
[217]Johnston L, J.Leger, J.Gelander, et al. Association between insulin-like growth factor I (IGF-I) polymorphisms, circulating IGF-I, and pre- and postnatal growth in two European small for gestational age populations[J]. J Clin Endocrinol Metab. 2003. 88(10):4805-4810.
[218]Zhou HM, A. D.McMurtry, J. P.Ashwell, et al. Insulin-like growth factor-I gene polymorphism associations with growth, body composition, skeleton integrity, and metabolic traits in chickens[J].Poult Sci. 2005.84(2):212-219.
[219]Taylor J, M. J.Bromage, N. R.Migaud, et al. Relationships between environmental changes,maturity, growth rate and plasma insulin-like growth factor-I (IGF-I) in female rainbow trout[J].Gen Comp Endocrinol. 2008.155(2):257-270.
[220]Amills MJ, N.Villalba, D.Tor, et al. Identification of three single nucleotide polymorphisms in the chicken insulin-like growth factor 1 and 2 genes and their associations with growth and feeding traits[J]. Poult Sci. 2003, 82(10):1485-1493.
[221]Maj AS, M.Siadkowska, E.Rowinska, B.Lisowski, et al. Polymorphism in genes of growth hormone receptor (GHR) and insulin-like growth factor-1 (IGF1) and its association with both the IGF1 expression in liver and its level in blood in Polish Holstein-Friesian cattle[J]. Neuro Endocrinol Lett 2008. 29(6):981-989.
[222]Wang GY, B.Deng, X.Li, et al. Insulin-like growth factor 2 as a candidate gene influencing growth and carcass traits and its bialleleic expression in chicken[J]. Sci China C Life Sci. 2005.48(2):187-194.
[223]Savage S, K.Walk, E.Modi, et al. Analysis of genes critical for growth regulation identifies Insulin-like Growth Factor 2 Receptor variations with possible functional significance as risk factors for osteosarcoma[J]. Cancer Epidemiol Biomarkers Prev. 2007. 16(8): 1667-1674.