奶山羊乳腺消减文库构建及差异表达基因的研究
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摘要
乳腺为哺乳动物新生儿的生长发育提供营养均衡的乳汁,并且可以为人类生活提供不可缺少的乳制品。在奶山羊的生理周期中乳腺组织经历发育、泌乳和退化三个循环过程,与此同时乳腺上皮细胞也历经增殖、分化,凋亡的变化。在奶山羊一个泌乳周期的不同阶段,产奶量的高低和乳成分的变化存在很大的差异,随着基因组学研究的不断深入,人们逐渐认识到导致这些差异产生的原因,是由乳腺组织中诸多相关功能基因时空表达决定的,即在不同泌乳期乳腺组织中的功能基因差异表达的结果。本研究在西农萨能奶山羊泌乳生理变化规律的基础上,构建不同泌乳期乳腺差异表达基因文库,克隆筛选到的差异表达基因,进行生物信息学分析和预测,采用实时定量PCR分析其表达模式,并对可能影响乳成分变化的重要候选基因骨桥蛋白(OPN)进行初步的探讨。为进一步研究奶山羊乳腺泌乳的分子机制,以及产奶量和乳成分调控机理提供理论依据。
1、利用抑制性消减杂交(SSH)技术构建西农萨能奶山羊泌乳初期和盛期乳腺组织正反(E-P和P-E)向差减cDNA文库,以管家基因GAPDH作为消减指标检测两个文库的消减效率分别为25和210倍,表明了泌乳初期和盛期乳腺组织中差异表达基因的富集效率也达到25倍以上；对E-P和P-E消减文库中部分差异表达基因进行测序,E-P文库测序分析后得到的差异表达基因按功能可大致分为：乳蛋白形成的相关基因(aS2酪蛋白、B酪蛋白、K酪蛋白、a乳白蛋白前体物),转录复合体相关基因(核糖体蛋白L10、核糖体蛋白L23、核糖体蛋白3B、Cbp/p300),能量代谢相关基因(NADH脱氢酶),细胞增殖分化相关基因(GHITM、OPN和H3F3B)；P-E文库中差异表达基因可分为：脂肪代谢相关基因(HFABP、PPARGClA),细胞生长代谢相关基因(SAA3、SSAT、SPARC和LPO),转录相关基因(剪接因子3B)；将奶山羊基因组中尚未克隆和研究的新基因PPARGClA、OPN、SPARC、GHITM和SSAT采用实时定量PCR进行验证,结果E-P文库中OPN、GHITM在泌乳初期乳腺组织中mRNA的表达丰度分别比泌乳盛期高5.04和4.20倍,P-E文库中PPARGCIA、SPARC、SSAT在泌乳盛期乳腺组织中mRNA的表达丰度分别比泌乳初期高3.58、12.13和8.0倍,均为阳性克隆。
2、根据不同物种间相同基因编码区的保守性和同源性序列设计合成引物,采用RT-PCR技术克隆了奶山羊乳腺中PPARGClA、OPN、SPARC、GHITM和SSAT基因的编码区序列,并提交Genbank获得登录号；利用在线多个生物信息学分析软件对山羊、牛、人和小鼠的PPARGClA、OPN、SPARC、GHITM和SSAT基因编码的蛋白质进行结构和功能预测,结果发现五个基因在不同物种间氨基酸序列高度同源,所编码的蛋白质结构、跨膜螺旋、信号肽和潜在功能位点大致相同。其中PPARGClA是一种转录调控因子,各物种均预测含有N端的转录激活区、核激素相互作用的LXXLL基序及C端的RNA识别基序；OPN是亲水性的分泌型糖蛋白,在不同的物种OPN均普遍存在RGD基序,该基序与细胞聚集、黏附、增殖及组织重塑等有关,山羊OPN比人和小鼠多cAMP依赖的蛋白激酶磷酸化位点,凝集因子VLSPR重复位点；SPARC是一种小分子的糖蛋白,结构域N端274-286处含有EF-hand钙结合位点,可能与乳腺中钙的代谢有关；GHITM是一种跨膜蛋白,有8个强跨膜区域,推测该基因可能与乳成分的跨膜转运有关；SSAT是细胞内维持代谢平衡的关键酶,有1个Gcn5-乙酰胺基转移酶功能域与SSAT的催化作用密切相关。
3、以β-actin为内标,采用实时定量PCR技术测定西农萨能奶山羊在一个泌乳周期(泌乳初期、盛期、中期、后期、末期和干奶期)中PPARGCIA、OPN、SPARC、GHITM和SSAT基因的表达丰度变化规律,结果表明：PPARGCIA和SSAT基因的变化趋势与泌乳曲线基本一致,推测它们是乳腺泌乳周期性变化的调节因子；OPN在泌乳初期的表达丰度相对值最高,依次是泌乳后期、末期、盛期、中期和干奶期,其中泌乳初期相对表达水平约为末期高3.9倍左右,进一步说明,在妊娠后期OPN基因就开始表达,OPN基因可能在乳成分变化中发挥重要的生理功能；SPARC在泌乳初期的表达丰度相对值最高,随后一直下降,在干奶期表达量最低；GHITM在泌乳初期的表达丰度相对值最高,依次是泌乳后期、盛期、末期和干奶期表达量最低。
4、构建OPN基因真核表达重组质粒pcDNA3.1/myc-His(-)A-OPN,与空质粒同时转染MCF-7细胞,利用MTT试验检测OPN基因对MCF-7细胞生长的影响,结果表明：转染pcDNA3.1-OPN细胞比转染pcDNA3.1细胞和对照细胞组活性明显升高,细胞的生长速度明显加快(P<0.05),且转染目的基因组pcDNA3.1-OPN的细胞增殖率为111.4%,高于未转染目的基因组pcDNA3.1的101.3%,说明OPN基因的表达对MCF-7细胞的增殖具有促进作用。
Mammary gland, which provide nutritious milk for growth and development of newborn mammals, while human life is indispensable to provide dairy products. The cycle of mammary gland has development, lactation and involution of the three processes, during each cycle mammary epithelial cell experience the process of proliferation, differentiation and cell apoptosis. The milk component and milk yield are greatly changed in the different lactation stages of dairy goat. With the study of knowledge on genomics, people gradually recognized that these changes are determined and regulated by a series of functional genes expression during the temporal and spatial in mammary gland. The paper is based of the lactation physiological changes in Xinong Saanen dairy goat. Screening, cloning and functional analysis of differentially expressed genes will elucidate the molecular of mammary gland. Suppression subtractive hybridization(SSH) method is used to isolate differently expressed genes in mammary gland of difference lactation stage stage of the Xinong Saanen goat(Capra hircus),further clone the differently expressed genes and predict their structure and function by bioinformatics,study the function of osteopontin (OPN) gene which is one of the different expression candidate genes. For further study of the molecular mechanisms of lactation, the milk production and milk composition provide a theoretical basis.
1. Suppression subtractive hybridization(SSH) technology is used to isolate differently expressed genes in mammary gland of early lactation stage and peak stage of the Xinong Saanen goat(Capra hircus).Some differently expressed genes were sequenced and analyzed.The new genes of dairy goat were searched and studied. Forward and reverse subtracted differently expressed cDNA library (E-P and P-E) were successfully created in mammary gland of different lactation. The subtraction efficiency was confirmed by a housekeeping gene named GAPDH,the results indicated that GAPDH was subtracted efficiently at 25 and 210 folds for E-P and P-E subtracted cDNA library respectively. Partial clone of E-P subtracted cDNA library were sequenced, we found that E-P library mainly included four groups of functional genes:milk protein related genes (αs2,βand K-casein, a-lactalbumin precursors), transcription complex genes(ribosomal protein L10,L23,3B and Cbp/p300),cell energy supplement genes NADH,cell proliferation and differentiation genes (GHITM、OPN and H3F3B).P-E library mainly included three groups of functional genes: milk fat metabolism related genes (HFABP、PPARGC1A),cell growth metabolism related genes (SAA3、SSAT、SPARC and LPO) and transcription related genes (splice factor 3B). Real-time reverse transcriptase-polymerase chain reaction was used to analyse the change of mRNA expression level of OPN and GHITM form E-P subtracted cDNA library. The results showed that they had 5.04 and 4.20 folds higher in early lactation stage than that in peak lactation stage. The change of mRNA expression level of PPARGCIA、SPARC and SSAT form P-E subtracted cDNA library had 3.58、12.13 and 8.0 folds higher in peak lactation stage than that in early lactation stage.
2. We designed primers based on the high homology sequence in gene coding region among different species and existed sequence for goat, the CDs region of PPARGC1A、OPN、 SPARC、GHITM and SSAT genes were cloned and sequenced from the goat mammary gland by RT-PCR, bioinformatics were employed to predict gene specific structure and function. The structure and function of PPARGC1A、OPN、SPARC、GHITM and SSAT were compared among goat, bovine, human, and mouse using bioinformatics software. The putative signal sequences, transmembrane domain, secondary and tertiary structure of five proteins were predicted by way of bioinformatics. The different species have their characteristics. The peroxysome proliferator-activated receptor gamma coactivator-lalpha(PGCla) is transcriptional coactivators consisting of N-terminal transcriptional activation domains and nuclear hormone receptor-interacting motif (LXXLL) and C-terminal RNA processing motifs that plays a central role in the regulation of cellular energy metabolism. OPN protein is secreted hydrophilic glycoprotein. In different species of OPN have RGD motif, which is correlated with the accumulation and cell adhesion, proliferation and tissue remodeling. Goat OPN had two additional potential binding motifs:cAMP-dependent protein kinase phosphorylation site and agglutination factor V LSPR repeat loci compared to humans'and mice. SPARC is a glycoprotein of small molecule, including N-terminal domain and EF-hand calcium-binding site, which may be related to calcium metabolism in mammary gland. GHITM is a transmembrane protein, there are eight strong transmembrane region, suggesting the gene may be associated with milk-related ingredients transmembrane. SSAT is the key enzyme of the cell metabolic balance and a Gcn5-acetyl-amino-transferase domain is closely related to SSAT of the catalytic effect.
3. Using beta-actin gene as the internal control, the SYBR Green quantitative real-time PCR (QPCR) analysis were conducted to determine the mRNA expression of PPARGC1A、OPN, SPARC、GHITM and SSAT genes in mammary gland at 28th,60th,100th,190th,270th and 330th day after kidding. The results showed that the expression trends of PPARGCIA and SSAT genes were similar with goat lactation curve, the dairy goat mammary gland increased milk yield dramatically during the first time of lactation, as evident from the marked increase in expression during the onset of lactation. PGCla mRNA expression reached the highest level on day 100, and subsequently decreased to a very low level on day 330. The expression on day 100 is about 13 folds (P< 0.01) of that on day 330. The results indicated that OPN gene exhibited the higher expression level in early (28 d) and late (190 d) lactation and the lowest level in dry period (330 d), which demonstrated a high-low-high-low pattern.SPARC gene exhibited the highest expression level in early (28 d) and late (190 d) lactation and subsequently decreased to a very low level on day 330.GHITM gene exhibited the highest expression level in early (28 d) subsequently decreased during the lactation of late, peak, end and dry periods.
4. Recombinant plasmid of pcDNA3.1-OPN was constructed by inserting the fragment of OPN gene into eukaryotic expression vector pcDNA3.1 and used to transfect the MCF-7 cell line following the restrictive endonuclease cleavage and sequence identification of the target gene segment, the effect of OPN gene on MCF-7 cell proliferation was assessed by MTT analysis. There was a significant difference (P< 0.05) in the proliferation between OPN gene transfect and non-transfect MCF-7 cells, it is suggested that the expression of OPN gene could stimulate the proliferation of MCF-7 cells. The growth rates of the OPN gene transfect is 111.4% while non-transfect MCF-7 cells is 101.3%.
1、利用抑制性消减杂交(SSH)技术构建西农萨能奶山羊泌乳初期和盛期乳腺组织正反(E-P和P-E)向差减cDNA文库,以管家基因GAPDH作为消减指标检测两个文库的消减效率分别为25和210倍,表明了泌乳初期和盛期乳腺组织中差异表达基因的富集效率也达到25倍以上；对E-P和P-E消减文库中部分差异表达基因进行测序,E-P文库测序分析后得到的差异表达基因按功能可大致分为：乳蛋白形成的相关基因(aS2酪蛋白、B酪蛋白、K酪蛋白、a乳白蛋白前体物),转录复合体相关基因(核糖体蛋白L10、核糖体蛋白L23、核糖体蛋白3B、Cbp/p300),能量代谢相关基因(NADH脱氢酶),细胞增殖分化相关基因(GHITM、OPN和H3F3B)；P-E文库中差异表达基因可分为：脂肪代谢相关基因(HFABP、PPARGClA),细胞生长代谢相关基因(SAA3、SSAT、SPARC和LPO),转录相关基因(剪接因子3B)；将奶山羊基因组中尚未克隆和研究的新基因PPARGClA、OPN、SPARC、GHITM和SSAT采用实时定量PCR进行验证,结果E-P文库中OPN、GHITM在泌乳初期乳腺组织中mRNA的表达丰度分别比泌乳盛期高5.04和4.20倍,P-E文库中PPARGCIA、SPARC、SSAT在泌乳盛期乳腺组织中mRNA的表达丰度分别比泌乳初期高3.58、12.13和8.0倍,均为阳性克隆。
2、根据不同物种间相同基因编码区的保守性和同源性序列设计合成引物,采用RT-PCR技术克隆了奶山羊乳腺中PPARGClA、OPN、SPARC、GHITM和SSAT基因的编码区序列,并提交Genbank获得登录号；利用在线多个生物信息学分析软件对山羊、牛、人和小鼠的PPARGClA、OPN、SPARC、GHITM和SSAT基因编码的蛋白质进行结构和功能预测,结果发现五个基因在不同物种间氨基酸序列高度同源,所编码的蛋白质结构、跨膜螺旋、信号肽和潜在功能位点大致相同。其中PPARGClA是一种转录调控因子,各物种均预测含有N端的转录激活区、核激素相互作用的LXXLL基序及C端的RNA识别基序；OPN是亲水性的分泌型糖蛋白,在不同的物种OPN均普遍存在RGD基序,该基序与细胞聚集、黏附、增殖及组织重塑等有关,山羊OPN比人和小鼠多cAMP依赖的蛋白激酶磷酸化位点,凝集因子VLSPR重复位点；SPARC是一种小分子的糖蛋白,结构域N端274-286处含有EF-hand钙结合位点,可能与乳腺中钙的代谢有关；GHITM是一种跨膜蛋白,有8个强跨膜区域,推测该基因可能与乳成分的跨膜转运有关；SSAT是细胞内维持代谢平衡的关键酶,有1个Gcn5-乙酰胺基转移酶功能域与SSAT的催化作用密切相关。
3、以β-actin为内标,采用实时定量PCR技术测定西农萨能奶山羊在一个泌乳周期(泌乳初期、盛期、中期、后期、末期和干奶期)中PPARGCIA、OPN、SPARC、GHITM和SSAT基因的表达丰度变化规律,结果表明：PPARGCIA和SSAT基因的变化趋势与泌乳曲线基本一致,推测它们是乳腺泌乳周期性变化的调节因子；OPN在泌乳初期的表达丰度相对值最高,依次是泌乳后期、末期、盛期、中期和干奶期,其中泌乳初期相对表达水平约为末期高3.9倍左右,进一步说明,在妊娠后期OPN基因就开始表达,OPN基因可能在乳成分变化中发挥重要的生理功能；SPARC在泌乳初期的表达丰度相对值最高,随后一直下降,在干奶期表达量最低；GHITM在泌乳初期的表达丰度相对值最高,依次是泌乳后期、盛期、末期和干奶期表达量最低。
4、构建OPN基因真核表达重组质粒pcDNA3.1/myc-His(-)A-OPN,与空质粒同时转染MCF-7细胞,利用MTT试验检测OPN基因对MCF-7细胞生长的影响,结果表明：转染pcDNA3.1-OPN细胞比转染pcDNA3.1细胞和对照细胞组活性明显升高,细胞的生长速度明显加快(P<0.05),且转染目的基因组pcDNA3.1-OPN的细胞增殖率为111.4%,高于未转染目的基因组pcDNA3.1的101.3%,说明OPN基因的表达对MCF-7细胞的增殖具有促进作用。
Mammary gland, which provide nutritious milk for growth and development of newborn mammals, while human life is indispensable to provide dairy products. The cycle of mammary gland has development, lactation and involution of the three processes, during each cycle mammary epithelial cell experience the process of proliferation, differentiation and cell apoptosis. The milk component and milk yield are greatly changed in the different lactation stages of dairy goat. With the study of knowledge on genomics, people gradually recognized that these changes are determined and regulated by a series of functional genes expression during the temporal and spatial in mammary gland. The paper is based of the lactation physiological changes in Xinong Saanen dairy goat. Screening, cloning and functional analysis of differentially expressed genes will elucidate the molecular of mammary gland. Suppression subtractive hybridization(SSH) method is used to isolate differently expressed genes in mammary gland of difference lactation stage stage of the Xinong Saanen goat(Capra hircus),further clone the differently expressed genes and predict their structure and function by bioinformatics,study the function of osteopontin (OPN) gene which is one of the different expression candidate genes. For further study of the molecular mechanisms of lactation, the milk production and milk composition provide a theoretical basis.
1. Suppression subtractive hybridization(SSH) technology is used to isolate differently expressed genes in mammary gland of early lactation stage and peak stage of the Xinong Saanen goat(Capra hircus).Some differently expressed genes were sequenced and analyzed.The new genes of dairy goat were searched and studied. Forward and reverse subtracted differently expressed cDNA library (E-P and P-E) were successfully created in mammary gland of different lactation. The subtraction efficiency was confirmed by a housekeeping gene named GAPDH,the results indicated that GAPDH was subtracted efficiently at 25 and 210 folds for E-P and P-E subtracted cDNA library respectively. Partial clone of E-P subtracted cDNA library were sequenced, we found that E-P library mainly included four groups of functional genes:milk protein related genes (αs2,βand K-casein, a-lactalbumin precursors), transcription complex genes(ribosomal protein L10,L23,3B and Cbp/p300),cell energy supplement genes NADH,cell proliferation and differentiation genes (GHITM、OPN and H3F3B).P-E library mainly included three groups of functional genes: milk fat metabolism related genes (HFABP、PPARGC1A),cell growth metabolism related genes (SAA3、SSAT、SPARC and LPO) and transcription related genes (splice factor 3B). Real-time reverse transcriptase-polymerase chain reaction was used to analyse the change of mRNA expression level of OPN and GHITM form E-P subtracted cDNA library. The results showed that they had 5.04 and 4.20 folds higher in early lactation stage than that in peak lactation stage. The change of mRNA expression level of PPARGCIA、SPARC and SSAT form P-E subtracted cDNA library had 3.58、12.13 and 8.0 folds higher in peak lactation stage than that in early lactation stage.
2. We designed primers based on the high homology sequence in gene coding region among different species and existed sequence for goat, the CDs region of PPARGC1A、OPN、 SPARC、GHITM and SSAT genes were cloned and sequenced from the goat mammary gland by RT-PCR, bioinformatics were employed to predict gene specific structure and function. The structure and function of PPARGC1A、OPN、SPARC、GHITM and SSAT were compared among goat, bovine, human, and mouse using bioinformatics software. The putative signal sequences, transmembrane domain, secondary and tertiary structure of five proteins were predicted by way of bioinformatics. The different species have their characteristics. The peroxysome proliferator-activated receptor gamma coactivator-lalpha(PGCla) is transcriptional coactivators consisting of N-terminal transcriptional activation domains and nuclear hormone receptor-interacting motif (LXXLL) and C-terminal RNA processing motifs that plays a central role in the regulation of cellular energy metabolism. OPN protein is secreted hydrophilic glycoprotein. In different species of OPN have RGD motif, which is correlated with the accumulation and cell adhesion, proliferation and tissue remodeling. Goat OPN had two additional potential binding motifs:cAMP-dependent protein kinase phosphorylation site and agglutination factor V LSPR repeat loci compared to humans'and mice. SPARC is a glycoprotein of small molecule, including N-terminal domain and EF-hand calcium-binding site, which may be related to calcium metabolism in mammary gland. GHITM is a transmembrane protein, there are eight strong transmembrane region, suggesting the gene may be associated with milk-related ingredients transmembrane. SSAT is the key enzyme of the cell metabolic balance and a Gcn5-acetyl-amino-transferase domain is closely related to SSAT of the catalytic effect.
3. Using beta-actin gene as the internal control, the SYBR Green quantitative real-time PCR (QPCR) analysis were conducted to determine the mRNA expression of PPARGC1A、OPN, SPARC、GHITM and SSAT genes in mammary gland at 28th,60th,100th,190th,270th and 330th day after kidding. The results showed that the expression trends of PPARGCIA and SSAT genes were similar with goat lactation curve, the dairy goat mammary gland increased milk yield dramatically during the first time of lactation, as evident from the marked increase in expression during the onset of lactation. PGCla mRNA expression reached the highest level on day 100, and subsequently decreased to a very low level on day 330. The expression on day 100 is about 13 folds (P< 0.01) of that on day 330. The results indicated that OPN gene exhibited the higher expression level in early (28 d) and late (190 d) lactation and the lowest level in dry period (330 d), which demonstrated a high-low-high-low pattern.SPARC gene exhibited the highest expression level in early (28 d) and late (190 d) lactation and subsequently decreased to a very low level on day 330.GHITM gene exhibited the highest expression level in early (28 d) subsequently decreased during the lactation of late, peak, end and dry periods.
4. Recombinant plasmid of pcDNA3.1-OPN was constructed by inserting the fragment of OPN gene into eukaryotic expression vector pcDNA3.1 and used to transfect the MCF-7 cell line following the restrictive endonuclease cleavage and sequence identification of the target gene segment, the effect of OPN gene on MCF-7 cell proliferation was assessed by MTT analysis. There was a significant difference (P< 0.05) in the proliferation between OPN gene transfect and non-transfect MCF-7 cells, it is suggested that the expression of OPN gene could stimulate the proliferation of MCF-7 cells. The growth rates of the OPN gene transfect is 111.4% while non-transfect MCF-7 cells is 101.3%.
引文
[1]罗军,李建文,武永厚.中国山羊业现状及发展对策[J].中国畜牧杂志2005,41(5),55-58
[2]刘荫武,曹斌云.应用奶山羊生产学.轻工业出版社,1990.
[3]向钊,龙火生,杨公社,左福元.牛泌乳性状的QTL研究进展[J].黄牛杂志2002,7(128),39-41
[4]罗军,曹斌云,姚军虎.奶山羊发展现状与产业化前景展望[A].2006中国羊业进展[C].甘肃,兰州：第三届中国羊业发展大会,2006,74-78.
[5]呼格吉乐图,旭日干,王建国.我国山羊业存在问题及对策[J].畜牧兽医杂志,2007,26(1)：66-68.
[6]曹斌云,罗军,姚军虎.我国山羊奶发展战略及前景分析[J].畜牧兽医杂志,2007,26(1)：51-54.
[7]罗军.奶山羊繁育体系建设现状与思路.第五界中国羊业发展大会论文,2008
[8]Swaisgood H E.Review and update of casein chemistry[J]. J Dairy Sci.1993,76(10):3054-3061
[9]Lincoln D T, Waters M J, Breipohl W. Growth hormone receptor expression in the proliferating rat mammary gland [J]. Acta Histochem.1990,40(Suppl):47-49.
[10]Karen Plant, Mario Ikceda and Barlara K Vonderhaar. Role of growth hormone and insulin-like growth factor I in mammary development [J].Endocr.1993,133(4):1843-1848.
[11]Shackleton M,Vaillant F, Simpson K J, Sting J, Smyth G K.Generation of a functional mammary gland from a single stem cell[J]. Nature.2006,1(439)84-88
[12]Stingl J, Eirew P, Ricketson I. Purification and unique properties of mammary epithelial stem cells [J]. Nature.2006,2(439) 993-997
[13]Mark D A and Sandra Z H. Differential Hormonal Regulation and function of progesterone receptor isoforms in normal adult mouse mammary gland [J].Endocrinology.2007,5(148),2290-2300
[14]Capuco A V, Ellis S E, Hale S A. Lactation persistency:insights from mammary cell proliferation studies [J]. J Anim Sci,2003,81:18-31.
[15]Linzell J L and Peaker M. Mechanism of milk secretion [J]. Physiol Rev.1971,51:564-597
[16]Zulak I M and Keenan T W. Citrate accumulation by a Golgi apparatus-rich fraction from lactating bovine mammary gland [J]. Int J Biochem.1983,15:747-750.
[17]Wendrinska A, Addey C V P, Orange P R, Boddy L M, Hendry K A K and Wildy CJ. Effect of a milk fat globule membrane fraction on cultured mouse mammary cells [J]. Biochem Soc Trans.1993,21: 220-225
[18]Smtth-kirwin S M, O'connor D M, Johnston J, Delancye E, Hassink S G and Funanage V L. Leptin expression in human mammary epithelial cells in breast milk [J]. J Clin Endocrinol Metab.1998,83: 1810-1813.
[19]Mather IH and Keenan TW. Origin and secretion of milk lipids[J]. JAMA.1998,3:259-273.
[20]Margaret C N,Thomas B M and Isabel F. Hormonal regulation of mammary differentiation and milk secretion[J]. J Mammary Gland Biol Neoplasia.2002,1(7),49-66
[21]Shyamala G. Progesterone signaling and mammary gland morphogenesis [J]. J Mammary Gland Biol Neoplasia.1999,4:89-104.
[22]Topper Y J and Freeman S.Multiple hormone interactions in the developmental biology of the mammary gland [J]. Physiol Rev.1980 (60),1049-1106
[23]Margaret C N, Thomas B M and Isabel F.Hormonal regulation of mammary differentiation and milk secretion journal of mammary gland[J]. J Mammary Gland Biol Neoplasia.2002,1(7):49-66
[24]Bocchinfuso W P and Korach K S. Mammary gland development and tumorigenesis in estrogen receptor knockout mice [J]. J Mammary Gland Biol Neoplasia.1997,2:323-334.
[25]Capuco A V, Ellis S E, Hale S A. Lactation persistency:insights from mammary cell proliferation studies [J]. J Anim Sci.2003,81:18-31.
[26]Shamay A, Zeelon E, Ghez Z. Inhibition of casein and fat synthesis and alpha lactalbumin secretion by progesterone in explants from bovine lactating mammary glands [J]. J Endocrinol,1987,113:81-88.
[27]Kastner P, Krust A, Turcotte B. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B [J]. EMBO J,1990,9: 1603-1614.
[28]Schams D, Kohlenberg S, Amselgruber W. Expression and localization of estrogen and progesterone receptors in the bovine mammary gland during development, function and involution [J]. J Endocrinol, 2003,177:305-17.
[29]Delbecchi L, Miller N, Prud'homme C, Petitclerc D, Wagner G F and Lacasse P.17β-estradiol reduces milk synthesis and increases stanniocalcin gene expression in the mammary gland of lactating cows[J]. Liv Prod Sci.2005,12(98),57-66
[30]Delbecchi L, Lacasse P. Suppression of estrous cycles in lactating cows has no effect on milk production[J]. J Dairy Sci.2006,89(2):636-639
[31]Knight C H.Overview of prolactin's role in farm animal lactation[J]. Liv Prod Sci.2001,1(70):87-93
[32]Brockman J L, Schuler L A. Prolactin signals via Stat5 and Oct-1 to the proximal cyclin D1 promoter [J]. Mol Cell Endocrinol.2005,3(239):45-53
[33]Keiko M, Jonathan M S, Gilbert H S. Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium [J]. J Cell Biol.2001,4(155):531-542
[34]Boutinaud M and Jammes H. Growth hormone increases Stat5 and Statl expression in lactating goat mammary gland:a specific effect compared to milking frequency [J].Domest Anim Endocrinol.2004,11(27):363-378,
[35]Salama A A K, Such X, Caja G, Rovai M, Casals R, Albanell E.Effects of once versus twice daily milking throughout lactation on milk yield and milk composition in dairy goats[J].J Dairy Sci. 2003,86:1673-1680
[36]Yamaji D, Kimura K, Watanabe A. Bovine hepatocyte growth factor and its receptor c-Met:cDNA cloning and expression analysis in the mammary gland[J].Domest Anim Endocrinol.2006,3(30):239-246
[37]Provost F L, Miyoshi K, Vilotte Jean-Luc, Bierie B.SOCS3 promotes apoptosis of mammary differentiated cells[J]. Biochem Biophys Res Commun.2005,338 (4),1696-1701
[38]Lambe T, Finlay D, Murphy M and Martin F. Differential expression of connexin 43 in mouse mammary cells[J]. Cell Biol Int.2006,5(30):472-479
[39]Akers R M, Ellis S E and Berry S D. Ovarian and IGF-Ⅰ axis control of mammary development in prepubertal heifers [J]. Domest Anim Endocrinol.2005,8(29):259-267
[40]Akers R M.Major Advances associated with hormone and growth factor regulation of mammary growth and lactation in dairy cows[J].J Dairy Sci.2006,89:1222-1234
[41]Sinowatz F, Schams D, Habermann F, Berisha B and Vermehren M.Localization of fibroblast growth factor Ⅰ (acid fibroblast growth factor) and its mRNA in the bovine mammary gland during mammogenesis, lactation and involution[J].Anat Histol Embryol.2006,35(3):202-207
[42]Emmanuelle F, Nora H, John G, Vesa K. Differential expression of TGF-β isoforms during postlactational mammary gland involution[J]. Cell Tissue Res.2000,300:89-95
[43]Plath A, Einspanier R,Peters F, Sinowatz F, Schams D. Expression of transforming growth factors alpha and beta-1 messenger RNA in the bovine mammary gland during different stages of development and lactation[J]. J Endocrinol.1997,155:501-511
[44]Motyl T,Gajkowska B,Wojewodzka U,Wareski P, Rekiel A,Ploszaj T.Expression of apoptosis-related proteins in involuting mammary gland of sow[J]. Comp Biochem Physiol B Biochem Mol Biol.2001,128: 635-646
[45]Wareski P, Motyl T, Ryniewicz Z, Orzechowski A, Gajkowska B,Wojewodzka U, Ploszaj T. Expression of apoptosis related proteins in mammary gland of goat[J]. Small Rumin Res.2001,40:279-289
[46]Wilde C J, Addey C V P, Li P, Fernig D G. Programmed cell death in bovine mammary tissue during lactation and involution[J]. Exp Physiol.1997,82:943-953
[47]Kordon E C, Mcknight R A, Chamelli J, Lothar H, Glenn M, Gilbert H S. Ectopic TGF-β, expression in the secretory mammary epithelium induces early senescence of the epithelial stem cell population[J]. Developmental Biology.1995,168:47-61.
[48]Zarzynska J, Motyl T. Dissimilar effects of LY 294002 and PD 098059 in IGF-I-mediated inhibition of TGF-beta(1) expression and apoptosis in bovine mammary epithelial cells[J]. J Physiol Pharmacol.2005, 56:181-193.
[49]Zhang Y, Proenca R, Maffei M. Positional Cloning of the Mouse Obese Gene and Its Human Homologue [J]. Nature.1994,372:425-432.
[50]Aoki N, Kawamura M, Matsuda T.Lactation-dependent down regulation of leptin production in mouse mammary gland[J].Biochim Biophys Acta.1999,1427:298-306.
[51]Neville M C, Medina D, Monks J. The mammary fat pad[J]. J Mamm Gland Biol and Neoplasia.1998, 3:109-116.
[52]Xin H, Subhash C. Leptin-a growth factor in normal and malignant breast cells and for normal mammary gland development [J]. J Natl Cancer Inst.2002,94:1704-1711.
[53]Fantuzzi G, Faggioni R. Leptin in the regulation of immunity,inflammation and hematopoiesis [J]. J Leukoc Biol.2000,68 (4):437-446.
[54]李萌,李庆章.奶山羊乳腺中瘦素的信号转导通路.中国乳品工业.2008,10(36)：23-26
[55]Wilde C J, Addey C V, Bryson J M, Finch L M, Knight C H, Peaker M.Autocrine regulation of milk secretion[J]. Biochem Soc Symp.1998,63:81-90.
[56]McManaman J L, Margaret C. Mammary physiology and milk secretion[J]. Neville Advanced Drug Delivery Reviews.2003,55:629-641
[57]Mikaelian I, Hovick M, Silva K A, Burzenski L M.Expression of terminal differentiation proteins defines stages of mouse mammary gland development [J].Vet Pathol.2006,1(43):36-49.
[58]Jenness R. Composition and characteristics of goat milk:Review 1968 - 1979[J]. J Dairy Sci.1980,63: 1605-1630.
[59]Saini A L,Gill R S.Goat milk:an attractive alternate[J].Indian Dairyman.1991,42:562 —564.
[60]Peaker M. Mechanism of milk secretion:milk composition in relation to potential difference across the mammary epithelium [J] J Physiol.1977,270:489-505
[61]Jolivet G, Meusnier C, Chaumaz G. Extracellular matrix regulates alpha sl-casein gene expression in rabbit primary mammary cells and CCAAT enhancer binding protein (C/EBP) binding activity [J]. J Cell Biochem,2001,82(3):371-86.
[62]Kuo C B, Wu W, Xu X. Pseudophosphorylated prolactin (S179D PRL) inhibits growth and promotes beta-casein gene expression in the rat mammary gland [J]. Cell Tissue Res,2002,309(3):429-437,
[63]Yamashita H, Nevalainen M T, Xu J. Role of serine phosphorylation of Stat5a in prolactin-stimulated beta-casein gene expression [J]. Mol Cell Endocrinol,2001,183(1-2):151-163.
[64]Masson P L and Heremans J F. Lactoferrin in milk from different species [J]. Comp Biochem Physiol B.1971,39(1):119-129
[65]Baker E N, Anderson B F, Baker H M, Day C L, Haridas M, Norris G E, Rumball S V, Smith C A and Thomas D H.Three-dimensional structure of lactoferrin in various functional states[J]. Adv Exp Med Biol.1994,1(357):1-12.
[66]Masson P L, Heremans J F and Schonne E. Lactoferrin, an iron-binbing protein nineutrophilic leukocytes[J] J Exp Med.1969,9(130):643-658.
[67]Cramer E, Pryzwansky K B, Villeval J L, Testa U and Breton-Gorius J. Ultrastructural localization of lactoferrin and myeloperoxidase in human neutrophils by immunogold[J]. Blood.1985,65:423-432.
[68]Otto B R, AM Verweij-van Vught and MacLaren D M. Transferrins and heme-compounds as iron sources for pathogenic bacteria [J], Crit Rev Microbiol.1992,18(3):217-33.
[69]Goodman R E and Schanbacher F L. Bovine lactoferrin mRNA:sequence, analysis, and expression in the mammary gland [J].Biochem Biophys Res Commun.1991,180(1):75-84.
[70]Reichenstein M, German T, Barash I. BLG-el-A novel regulatory element in the distal region of the β-lactoglobulin gene promoter[J].FEBS Letters.2005,10 (579) 2097-2104
[71]Moioli B, Napolitano F, Orru L, Catillo G Single nucleotide polymorphism detection in promoter III of the acetyl-CoA carboxylase-alpha gene in sheep[J].J Anim Breed Genet.2005,122(6):418-20.
[72]Hanigan M D, Cant J P, Weakley D C and Beckett J L. An evaluation of postabsorptive protein and amino acid metabolism in the lactating dairy cow [J]. J Dairy Sci.1998,81 (12):3385-3401。
[73]Peel C J, Taylor J W. Robinson I B and Hooley R D.The use of oestrogen, progesterone and reserpine in the artificial induction of lactation in cattle[J].Aust J Biol Sci.1979,32 (2):251-259.
[74]Davis S R, Collier R J, McNamara J P, Head H H and Sussman W. Effects of thyroxine and growth hormone treatment of dairy cows on milk yield, cardiac output and mammary blood flow [J]. J Anim Sci.1988,66:70-79.
[75]Bremmer D R, Overton T R and Clark J H.Production and composition of milk from jersey cows administered bovine somatotropin and fed ruminally protected amino acids[J]J Dairy Sci.1997,80:1374-1380.
[76]Mcguire M A, Griinari J M, Dwyer D A and Bauman D E. Role of insulin in the regulation of mammary synthesis of fat and protein[J] J Dairy Sci.1995,78:816-824.
[77]Griinari J M, McGuire M A, Dwyer D A, Bauman D E and Palmquist D L. Role of insulin in the regulation of milk fat synthesis in dairy cows[J]J Dairy Sci.1997,80:1076-1084.
[78]Griinari J M, Mcguire M A, Dwyer D A, Bauman D E, Barbano D M and House W A. The role of insulin in the regulation of milk protein synthesis in dairy cows[J].J Dairy Sci.1997,80 (10):2361-2371
[79]Moioli B, Pilla F and Tripaldi C. Detection of milk protein genetic polymorphisms in order to improve dairy traits in sheep and goats:a review[J]. Small Rumin Res.1998,3(27):185-195
[80]Dinesh K, Neelam G, Ahlawat S P S, Satyanarayana R,Shyam Sunder, Gupta S C.Single strand confirmation polymorphism (SSCP) detection in exon I of the a-lactalbumin gene of Indian Jamunapari milk goats (Capra hircus)[J]. Genet Mol Biol.2006,2(28):287-293
[81]Martin P, Szymanowska M, Zwierzchowski L, Christine L,Eroux C.The impact of genetic polymorphisms on the protein composition of ruminant milks [J]. Reprod Nutr Dev.2002,42(5):433-459
[82]陈宏,蓝贤勇,李瑞彪,雷初朝,孙维斌,张润锋,郑元林,朱必才CSN1S2、 CSN3和β-1g基因对西农萨能奶山羊产奶性能的影响.遗传学报.2005,32(8)：804-810
[83]Robinson G W, McKnight R A, Smith G H. Mammary epithelial cells undergo secretory differentiation in cycling virgins but require pregnancy for the establishment of terminal differentiation.Development[J].1995,121:2079-2090
[84]Chilliard Y, Ferlay A, Rouel J and Lamberet G. A review of nutritional and physiological factors affecting goat milk lipid synthesis and lipolysis[J]. J Dairy Sci.2003,86:1751-1770
[85]Parodi P W.Conjugated linoleic acid and other anticarcinogenic agents of bovine milk fat[J]. J Dairy Sci.1999,82:1339-1349
[86]Sebedio J L, Gnaedig S and Chardigny J M. Recent advances in conjugated linoleic acid research[J]. Curr Opin Clin Nutr Metab Care.1999,2:499-506.
[87]Williams C M. Dietary fatty acids and human health [J]. Ann Zootech.2000,49:165-180
[88]Sanz Sampelayo M R, Chilliard Y, Schmidely Ph and Boza J. Influence of type of diet on the fat constituents of goat and sheep milk [J]. Small Rumin Res.2007,3(68) 42-63
[89]Reh W A, Maga E A, Collette N M B, Moyer A. Using a Stearoyl-CoA desaturase transgene to alter milk fatty acid composition [J]. J Dairy Sci.2004,87:3510-3514
[90]Liang P, Pardee A B. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction [J]. Science.1992,257(14):967-971
[91]Hubankm, Schatz D G. Identifying differences in mRNA expression by resentational difference analysis of cDNA [J]. Nucleic Acids Res.1994,22:5640-5648
[92]Diatchenko L, Lukyanov S, Lau Y F. Suppression subtractive hybridization:a versatile method for identifying differentially expressed genes [J]. Methods Enzymol.1996,303:349-380.
[93]Yang G P, Ross D T. Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes[J].Nucleic Acids Res.1999,27:1517-1523.
[94]邱志鹏,王种.抑制消减杂交及其应用.生物技术通报.2006年增刊246-250
[95]Adams M D, Kelley J M, Gocayne J D, Dubnick M, Polymeropoulos M H, Xiao H, Merril C R, Wu A, Olde B, Moreno R F. Complementary DNA sequencing expressed sequence tags and human genome project [J].Science.1991,252(5013):1651-1656
[96]Schena M, Shalon D, Davis R W, Brown P O.Quantitative monitoring of gene expression patterns with a complementary DNA microarray[J]. Science.1995,270:467-470
[97]Schulze A. From membranes to chips—a pocket guide to DNA microarray technology:DNA microarrays:gene expression applications [J]. J Cell Sci.2002,115:1781-1785
[98]Veluculescu V E, Zhang L, Vogestein B, Kinzler K W.Serial analysis of gene expression [J]. Science.1995,270:484-487
[99]Ishii M, Hashimoto S, Tsutsumi S, Wada Y, Matsushima K, Kodama T, Aburatani H. Direct comparison of gene chip and SAGE on the quantitative accuracy in transcript profiling analysis [J]. Genomics.2000,68:136-143
[100]Andrade M A, Sander C. Bioinformatics:from genome data to biological knowledge[J].Curr Opin Biotechnol.1997,8:675-683.
[101]Luscombe N M, Greenbaum D, Gerstein M. What is bioinformatics? A proposed definition and overview of the field[J]. Methods Inf Med.2001,40:346-358.
[102]Bonetta L. Bioinformatics-from genes to pathways[J]. Nat Methods.2004,1:169-176.
[103]Bichet A, Polverari D, Malpertuy A. Gene regulation and bioinformatics[J]. Bull Cancer.2005,92: 97-107.
[104]蒋彦,王小行,曹毅等.基础生物信息学及应用[M].北京：清华大学出版社,2003.
[105]王亚辉.世纪之交生物学发展的主要趋势[J].中国科学基金,2000,(3)：167-168
[106]张春霆.生物信息学的现状与展望[J].世界科技研究与发展,2000,(6)：17-20
[107]Amand K B, Terrance E M. Evolutionary analysis by whole genome comparisons [J]. J Bacteriol.2002, (8):2260-2272
[108]Andrada M A,Sander C.Bioinformatics from genome data to biological knowledge[J]. Current Opinion Biotechnol.1997, (6):675-683
[109]Persson B. Bioinformatics in protein analysis [J]. EXS.2000,(88):215-231
[110]da Silveira N J, Uchoa H B, Canduri F, Pereira J H, Camera J C J, Basso L A, Palma M S, Santos D S, de Azevedo W.J.Structural bioinformatics study of PNP from Schistosoma mansoni [J].Biochem Biophys Res Commun.2004, (1):100-104
[111]Geourjon C and Deleage G, SOPMA:significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments[J]. Comput Appl Biosci.1995,11 (6):681-684
[112]Papin J,Subramaniam S.Bioinformatics and cellular signaling[J].Curr Opin Biotechnol.2004,(1):78-81
[113]廖问陶,赵志伟,王茂林.诸葛菜(Orychophragmus violaceus)Toc33基因编码区的克隆及序列分析.四川大学学报(自然科学版),2003,40(1)：163-167.
[114]Raghothama C, Harsha H C, Prasad C K, Pandey A. Bioinformatics and proteomics approaches for aging research[J].Biogerontology.2005,6:227-232
[115]Read T D, Salzberg S L, Pop M, Shumway M, Umayam L, Jiang L, Holtzapple E, Busch J D, Smith K L, Schupp J M, Solomon D, Keim P, Fraser C M. Comparative genome sequencing for discovery of novel polymorphisms in Bacillus anthracis[J].Science,2002,296(5575):2028-2033
[116]Andreas D.Baxevanis, Francis Ouellette B F著,李衍达,孙之荣等译.生物信息学,北京：清华大学出版社,2000
[117]Laurent P, Elduque C, Hayes H, Saunier K, Eggen A and Leveziel H. Assignment of 60 human ESTs in cattle[J]. Mamm Genome.2000,11 (9):748-754
[118]Adams M D, Kelley J M, Gocayne J D, Dubnick M, Polymeropoulos M H, Xiao H, Merril C R,Wu A, Olde B, Moreno R F. Complementary DNA sequencing:expressed sequence tags and human genome project[J]. Science.1991,252:1651-1656
[119]Smith E, Shi L, Drummond P, Rodriguez L, Hamilton R, Powell E, Nahashon S, Ramlal S, Smith G, Foster J. Development and characterization of expressed sequence tags for the turkey (Meleagris gallopavo) genome and comparative sequence analysis with other birds [J]. Anim Genet.2000,31:62-67
[120]Millar A H, Whelan J, Small I.Recent surprises in protein targeting to mitochondria and plastids[J]. Curr Opin Plant Biol.2006,9:610-615
[121]Houdebine LM. Transgenic animal bioreactors [J]. Transgenic Res,2000,9(45),305-320
[122]Bionaz M and Loor J J. Identification of reference genes for quantitative real-time PCR in the bovine mammary gland during the lactation cycle [J]. Physiol Genomics.2007,5(29):312-319.
[123]Holland M S and Holland R E.The cellular perspective on mammary gland development: stem/progenitor cells and beyond [J]. J Dairy Sci.2005,88:E1-E8.
[124]Capuco A V, Wood D L, Baldwin R. Mammary cell number, proliferation and apoptosis during a bovine lactation:relation to milk production and effect of bST[J]. J Dairy Sci.2001a,84:2177-2187.
[125]Livak K J and Schmittgen T D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method[J]. Methods.2001,25:402-408
[126]黄涛,熊远著,徐德全,邓昌彦,雷明刚,蒋思文,郑嵘,姜勋平,李凤娥,李家连,左波.大梅与梅山猪背最长肌正反消减文库的构建及序列分析[J].农业生物技术学报.2006,14(4)：456-461.
[127]曹随忠,李宏滨,王爱华,赵兴绪,杜立新.抑制性消减杂交(SSH)构建乳房炎奶牛外周血白细胞差异表达cDNA文库[J].畜牧兽医学报.2005,36(6)：526-530.
[128]Jenness R. Biochemical and nutritional aspects of milk and colostrum.1985:The Iowa State University Press.164-197.
[129]Ferranti P, Malorni A, Nitti GPrimary structure of ovine alpha sl-caseins:localization of phosphorylation sites and characterization of genetic variants A, C and D[J]. J Dairy Res.1995, 62(2):281-296.
[130]Martin P, Szymanow S M, Zwierzchow S L, Christine L,Eroux C.The impact of genetic po lymorphisms on the prote in composition of ruminant milks[J]. Rep rod Nutr Dev,2002,42 (5):433-459.
[131]Yahyaoui M H, Ang iolillo A, Pilla F, Sanche Z A, Folch J.Characterization and genotyping of the caprine K2casin variantsfJ]. J Dairy Sci,2003,86:2715-2720.
[132]Mackinlay A G W. Milk Proteins, Chemistry and Molecular Biology.1971, New York:Academic Press.172-215.
[133]Shekar P C, Goel S, Rani S D.kappa-casein-deficient mice fail to lactate[J].Proc Natl Acad Sci USA.2006,103(21):8000-8005.
[134]Chanat E, Martin P, Ollivier-Bousquet M. Alpha(Sl)-casein is required for the efficient transport of beta-and kappa-casein from the endoplasmic reticulum to the Golgi apparatus of mammary epithelial cells[J]. J Cell Sci.1999,112:3399-3412.
[135]Svensson M, Hakansson A, Mossberg A K.Conversion of alpha-lactalbumin to a protein inducing apoptosis[J]. Proc Natl Acad Sci USA.2000,97(8):4221-4226.
[136]Kuss A W, Gogo 1 J. Geidermann H.Associations of a polymorphic AP 22 binding site in the 5'flanking region of the bovine beta-lactoglobul in gene with milk proteins[J]. J Dairy Sci,2003,86 (6): 2213-2218.
[137]Jenness R. Biochemical and nutritional aspects of milk and colostrum.1985:The Iowa State University Press.164-197.
[138]Ferranti P, Carbone V, Sannolo N, Fiume I, Malorni A. Mass spectrometric analysis of rat hemoglobin by FAB-overlapping. Primary structure of the alpha-major and of four beta constitutive chains. Int J Biochem.1993,25(12):1943-1950
[139]Jessica Harris, Prudence M. Stanford, Kate Sutherland, Samantha R. Oakes, Matthew J. Naylor, Fiona G. Robertson, Katrina D. Blazek, Michael Kazlauskas, Heidi N. Hilton, Sergio Wittlin, Warren S lexander, Geoffrey J Lindeman, Jane E.Visvader, and Christopher J. Ormandy.Socs2 and Elf5 Mediate Prolactin-Induced Mammary Gland Development[J].Mol Endocrinol.2006,20(5):1177-1187
[140]Zhou J, Chehab R, Tkalcevic J, Naylor M J, Harris J,Wilson T J, Tsao S, Tellis I, Zavarsek S, Xu D, Lapinskas E J, Visvader J, Lindeman G J, Thomas R, Ormandy C J,Hertzog P J, Kola I, Pritchard M A. Elf5 is essential for early embryogenesis and mammary gland development during pregnancy and lactation[J]. EMBO J.2005,24:635-644
[141]Tadashi Y, Shinji N, Hiroshi K.Ghitm is an ortholog of the Bombyx mori prothoracic gland-derived receptor (Pgdr) that is ubiquitously expressed in mammalian cells and requires an N-terminal signal sequence for expression[J]. Biochem Biophys Res Commun.2006,341:13-18
[142]Kerstin R, Claudia Y C, Vesna B, Peter M V.The Growth-hormone inducible transmembrane protein (Ghitm) belongs to the Bax inhibitory protein-like family[J]. Int J Biol Sci.2007,3(7):471-476
[143]Kayla J. Bayless, George E. Davis and Gerald A. Meininger. Isolation and biological properties of osteopontin from bovine milk[J]. Protein Expr Purif.1997,9:309-314.
[144]Leonard S, Khatib H, Schutzkus V. Effects of the osteopontin gene variants on milk production traits in dairy cattle[J]. J Dairy Sci.2005,88:4083-086.
[145]Takehiro Ogata,Tomomi Ueyama,Tetsuya Nomura.Osteopontin is a myosphere-derived secretory molecule that promotes angiogenic progenitor cell proliferation through the phosphoinositide 3-kinase/Akt pathway[J]. Biochem Biophys Res Commun.2007,359:341-347.
[146]Gao Chengjiang, Mi Zhiyong, Guo Hongtao.Osteopontin regulates ubiquitin-dependent degradation of statl in murine mammary epithelial tumor cells[J]. Neoplasia.2007,9(9):699-706.
[147]Nemir M, Bhattacharyya D, Li Xiaoming.Targeted inhibition of osteopontin expression in the mammary gland causes abnormal orphogenesis and lactation deficiency[J].J Biol Chem.2000,275(2):969-976.
[148]Sorensen E S, Hojrup P and Petersen T E.Posttranslational modifications of bovine osteopontin: Identification of twenty-eight phosphorylation and three O-glycosylation sites[J]. Protein Sci. 1995,4:2040-2049.
[149]Albig W, BramLage B,Gruber K, Klobeck Hans-Gustav, Kunz J R and Doenecke D.The Human replacement histone H3.3B gene (H3F3B)[J].Genomics.1995,30:264-272
[150]Yang Y, Spitzer E, Kenney N, Zschiesche W, Li M, Kromminga A, Miiller T, Spener F, Lezius A, Veerkamp J H.Members of the fatty acid binding protein family are differentiation factors for the mammary gland[J].J Cell Biol.1994,127(4):1097-109.
[151]Binas B, Spitzer E, Zschiesche W, Erdmann B, Kurtz A, Mueller T, Niemann C, Blenau W, Grosse R Hormonal induction of functional differentiation and mammary derived growth inhibitor expression in cultured mouse mammary gland explants[J]. In Vitro Cell Dev Biol.1992,28:625-634
[152]Heuckeroth R O, Birkenmeier E H, Levin M S, Gordon J I.Analysis of the tissue-specific expression, developmental regulation, and linkage relationships of a rodent gene encoding heart fatty acid binding protein[J].J Biol Chem.1987,262:9709-9717
[153]Puigserver P, Spiegelman B M. Peroxisome proliferators activated receptor-gamma coactivator 1 alpha (PGC-lalpha):Transcriptional coactivator and metabolic regulator [J]. Endocrinol Rev.2003,24(1), 78-90.
[154]Zhang Q, Boichard D, Hoeschele I, Ernst C, Eggen A, Murkve B, Pfister-Genskow M,Witte L A, Grignola F E, Uimari P, Thaller G, Bishop M D.Mapping quantitative trait loci for milk production and health of dairy cattle in a large outbred pedigree[J]. Genetics.1998,149:1959-1973.
[155]Knutti D,Kralli A.PGC-1:a versatile coactivator [J].Trends Endocrinol and Metab.2001,12(8), 360-365.
[156]Urieli-Shoval S, Linke R P, Matzner Y. Expression and function of serum amyloid A, a major acute phase protein, in normal and disease states [J]. Curr Opin Hematol.2000,7:64-69.
[157]朱大龙,童国玉.血清淀粉样蛋白A-联系肥胖及其代谢合并症的促炎性脂肪细胞因子[J].国际代谢杂志,2006,26(3)：205-210
[158]Pruzanski W, de Beer F C, de Beer M C. Serum amyloid A protein enhances the activity of secretory non-pancreatic phospholipase A2[J]. J Biochem.1995,309:461-464.
[159]Preciado Patt L, Hershkoviz R, Fridkin M. Serum amyloid A binds specific extracellular matrix glycoproteins and induces the adhesion of resting CD4+T cells [J]. J Immunol.1996,156:1189-1195.
[160]Ancsin J B, Kisilevsky R. Characterization of high affinity binding between laminin and the acute-phase protein, serum amyloid A [J]. J Biol Chem.1997,272:406-413.
[161]Baranova I N, Vishnyakova T G, Bocharov A V. Serum amyloid a binding to CLA-1 (CD36 and L IMPII analogous-1) mediates serum amyloid a protein induced activation of ERK1/2 and p38 mitogen-activated protein kinases [J]. J Biol Chem.2005,280:8031-8040.
[162]Casero R A Jr, Pegg A E. Spermidine/spermine N1-acetyltransferase the turning point in polyamine metabolism[J]. FASEB J.1993,7:653-661.
[163]Schluter K D, Frischkopf K, Flesch M. Central role for ornithine decarboxylase in β-adrenoceptor mediated hypertrophy[J].Cardiovasc Res.2000,45(2):410-417.
[164]Kremzner L T. Metabolism of polyamines in the nervous system[J]. Fed Proc.1970,29:1583-1588.
[165]Seiler N,Bolkenius F N.Polyamine reutilization and turnover in brain[J].Neurochem Res. 1985,10:529-544.
[166]Vujcic S, Halmekyto M, Diegelman P, Gan G, Kramer D L, Janne J and Porter C W.Effects of Conditional Overexpression of Spermidine/Spermine N1-Acetyltransferase on Polyamine Pool Dynamics, Cell Growth,and Sensitivity to Polyamine Analogs. J Biol Chem.2000,275(49)38319-38328,
[167]Thomas T, Thomas T J. Polyamines in cell growth and cell death:molecular mechanisms and therapeutic applications [J]. Cell Mol Life Sci.2001,58:244-258.
[168]Babu G N, Sailor K A, Sun D. Spermidine/spermine N1-acetyl transferase activity in rat brain following transient focal cerebral ischemia and reperfusion [J]. Neurosci Lett.2001,300(1):17-20.
[169]Brekken R A, Sage E H. SPARC, a matricellular protein:at the crossroads of cell matrix[J]. Matrix Biol.2000,19(7):569-580.
[170]Francki A, Motamed K, McClure T D. SPARC regulates cell cycle progression in mesangial cells via its inhibition of IGF dependent signaling [J]. J Cell Biochem.2003,88(4):802-811.
[171]Zhou X, Tan F K, Guo X. Small interfering RNA inhibition of SPARC attenuates the profibrotic effect of transforming growth factor betal incultured normal human fibroblasts[J].Arthritis Rheum.2005,52 (1):257-261.
[172]Tadashi U, Kazuhiro S, Tetsuo K, Ikuya Y and Shigekazu N.Molecular cloning and characterization of the chromosomal gene for human lactoperoxidase[J].Eur J Biochem.1997,243,32-41
[173]Lesk AM. Introduction to Bioinformatics [M].1st ed. New York:Oxford University Press.2002, 1-61.
[174]冯浩咏,苗向阳,罗绪刚,胡婕.生物信息学在发现新基因方面的应用.生物技术学报.2007,5：1-5
[175]唐旭清,朱平.后基因组时代生物信息学的发展趋势.生物信息学.2007,3：142-144
[176]Elisabeth G, Alexandre G, Christine H. ExPASy:the proteomics server for in-depth protein knowledge and analysis[J]. Nucleic Acids Res.2003,31(13):3784-3788
[177]成军,刘妍,陆荫英.生物信息学技术与新基因的研究[J].世界华人消化杂志,2003,11(4)：474-4771
[178]Wu Zhidan, Puigserver P, Andersson U, Adelmant G,Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC,Spiegelman B M. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1[J].Cell.1999,98(1):115-124.
[179]Morgan A, Burgoyne R D, Barclay J W. Regulation of exocytosis by protein kinase C[J]. Biochem Soc Trans.2005,33:1341-1344.
[180]Fields S, Song O. A novel genetic system to detect protein-protein interactions [J]. Nature.1989,340: 245-246
[181]Yamane K, Kinsella T J. Casein kinase 2 regulates both apoptosis and the cell cycle following DNA damage induced by 6-thioguanine [J]. Clin Cancer Res.2005,11:2355-2363.
[182]Sodek J, Ganss B, McKee M D.Osteopontin[J].Crit Rev Oral Biol Med.2000,11(3):279-303.
[183]Oldberg A, Franzen A, Heinegard D.Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence[J]. Proc Natl Acad Sci USA.1986,83: 8819-8823.
[184]Colombo S,Longhi R,Alcaro S.N-myristoylation determines dual targeting of mammalian NADH-cytochrome b5 reductase to ER and mitochondrial outermembranes by a mechanism of kinetic partitioning [J]. J Cell Biol.2005,168:735-745.
[185]Quinn P R O, Knabe D A and Wu G. Arginine catabolism in lactating porcine mammary tissue[J]. J Anim Sci.2002,80:467-474
[186]陈英剑,胡成进,赵苗青SYBR Green实时荧光定量PCR技术平台的建立.实用医药杂志,2004,21(11)：997-999.
[187]Overbergh L, Giulietti A, Valckx D. The use of real-time reverse transcriptase PCR for the quantification of cytokine gene expression[J]. J Biomol Tech.2003,14:33-43.
[188]Jain M, Nijhawan A, Tyagi A K, Khurana JP. Validation of housekeep ing genes as internal control for studying gene expression in rice by quantitative real-time PCR [J]. Biochem Biophy Res Commun.2006, 345:646-651.
[189]Wu G Q, Deng X M, Li J Y, Li N, Yang N. A potential molecular marker for selection against abdominal fatness in chickens[J]. Poult Sci.2006,85:1896-1899.
[190]Wiener P, Maclean I, Williams J L,Woolliams J A.Testing for the presence of previously identified QTL for milk production traits in new populations [J]. Anim Genet.2000,31:385-395.
[191]Weikard R, Kuhn C, Goldammer T, Freyer G, Schwerin M.The bovine PPARGC1A gene:Molecular characterization and association of an SNP with variation of milk fat synthesis [J]. Physiol Genomics. 2005,21:1-13.
[192]Georges M, Nielsen D, Mackinnon M, Mishra A, Okimoto R, Pasquino A T, Sargeant L S,Sorensen A,Steele M R, Zhao X, Womack J E, Hoeschele I. Mapping quantitative trait loci controlling milk production in dairy cattle by exploiting progeny testing[J].Genetics.1995,139:907-920.
[193]Freyer G, Sorensen P, Kuhn C, Weikard R, Hoeschele I.Search for pleiotropic QTL on chromosome BTA6 affecting yield traits of milk production[J]. J Dairy Sci.2003,86:999-1008.
[194]Bionaz M, Loor J J. Gene networks driving bovine milk fat synthesis during the lactation cycle[J].BMC Genomics.2008,9(1),366-423.
[195]Khatib H, Zaitoun I, Wiebelhaus-Finger J, Chang Y M, Rosa G J. The association of bovine PPARGC1A and OPN genes with milk composition in two independent Holstein cattle populations [J]. J Dairy Sci.2007,90 (6),2966-2970.
[196]Weikard R, Kuhn C, Goldammer T, Freyer G, Schwerin M. PPARGC1A a candidate gene for a QTL on BTA6 affecting milk fat synthesis.29th Int. Conf. Ani. Gen, ISAG,2004,60pp.
[197]Lin J, Yang R, Tarr P T. Hyperlipidemic effects of dietary saturated fats mediated through PGC-lbeta coactivation of SREBP[J]. Cell.2005,120:261-27
[198]Inman C K,Shore P.The osteoblast transcription factor Run-2 is expressed in mammary epithelial cells and mediates osteopontin expression[J]. J Biol Chem.2003,278(49):48684-48689.
[199]Bayless K J, Davis G E, Meininger G A. Isolation and biological properties of osteopontin from bovine milk[J]. Protein Expr Purif.1997,9:309-314.
[200]Miri C Z, Seroussi E, Larkin D M, Loor J J, Wind A E, Lee J H, Drackley J K, Band M R, Hernandez A G, Shani M, Lewin H A, Weller J I and Ron M. Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle [J]. Genome Res.2005,15:936-944
[201]Rittling S R and Novick K E. Osteopontin expression in mammary gland development and tumorigenesis[J]. Cell Growth Differ.1997,8(10),1061-1069
[202]Nagatomo T,Ohga S,Takada H, Nomura A, Hikino S, Imura M, Ohshima K and Hara T. Microarray analysis of human milk cells:Persistent high expression of osteopontin during the lactation period[J]. Clin Exp Immunol.2004,138(1):47-53
[203]Schnabel R D, Kim J, Ashwell M S, Sonstegard T S, Van Tassell C P, Connor E E and Taylor J F. Fine-mapping milk production quantitative trait loci on BTA6:Analysis of the bovine osteopontin gene[J]. PNAS.2005,102(19):6896-6901
[204]Cohen-Zinder M, Seroussi E, Larkin D M, Loor J J, Wind A E, Lee J H, Drackley J K, Band M R,Hernandez A G, Shani M, Lewin H A, Weller J I, Ron M.Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle[J].Genome Res.2005,15:936-944.
[205]Olsen H G, Nilsen H, Hayes B, Berg P R, Svendsen M, Lien S, Meuwissen T.Genetic support for a quantitative trait nucleotide in the ABCG2 gene affecting milk composition of dairy cattle[J]. BMC Genet. 2007,21:8-32.
[206]Sage E H, Vemon R, Decker J, Funk S, Iruela-Arispe M. Distribution of the calcium-binding protein SPARC in tissues of embryonic and adult mice[J]. J Histochem Cytochem 1989,37:819-834
[207]Peggy L P, E. Helene S, Timothy E L, Sarah E F and Allen M G. Distribution of SPARC in Normal and Neoplastic Human Tissue'[J]. J Histochem Cytochem.1995,8(43):791-800.
[208]Bauman D E, Everett R W,Weiland W H. Production responses to bovine somatotropin in northeast dairy herds [J]. J Dairy Sci.1999,82:2564-2573.
[209]Van Amburgh M E, Galton D M. Management and economics of extended calving intervals with use of bovine somatotropin [J]. Livest Prod Sci.1997,50:15-28.
[210]Knight C H, Fowler P A and Wilde C J. Galactopoietic and mammogenic effects of long-term treatment with bovine growth hormone and thrice daily milking in goats [J]. J Endocrinol.1990,127: 129-138.
[211]Capuco A V, Wood D L, Baldwin R. Mammary cell number, proliferation and apoptosis during a bovine lactation:relation to milk production and effect of bST[J]. J Dairy Sci.2001a,84:2177-2187.
[212]Singh K, Davis S R, Dobson J M, Molenaar A J, Wheeler T T, Prosser C G, Fair V C, Oden K, Swanson K M, Phyn C V C, Hyndman D L, Wilson T, Henderson H V and Stelwagen .K.cDNA microarray analysis reveals that antioxidant and immune genes are upregulated during involution of the bovine mammary gland [J]. J Dairy Sci.2008,91(6):2236-2246
[213]Anthony E Pegg.Spermidine/spermine-N-acetyltransferase:a key metabolic regulator[J].Am J Physiol Endocrinol Metab.2008,294:E995-E1010
[214]司徒镇强,吴军正.细胞培养[M].西安：世界图书出版社,2006
[215]杨芳,路国华,刘利兵,刘芳娥,曲萍.影响MTT比色试验的关键环节.第四军医大学学报.2009,30 (3)：243-247
[216]Sharp J A, Sung V, Slavin J, Thompson E W, Henderson M A.Tumor cells are the source of osteopontin and bone sialoprotein expression in human breast cancer[J]. Lab Invest.1999,79(7):869-877.
[217]Das Riku, Mahabeleshwar G H, Kundu G C.Osteopontin stimulates cell motility and nuclear factor B-mediated secretion of urokinase type plasminogen activator through phosphatidylinositol 3-kinase/akt signaling pathways in breast cancer cells[J]. J Biol Chem.2003,31(278):28593-28606.
[218]Laura K. Sickafoose, Qian J. Chen, Meghan B. Wood, Robert D. Cardiff, Jeffrey P. Gregg and Alexander D B. Osteopontin overexpression in the mouse mammary epithelium induces proliferation and potentates mammary carcinogenesis[J].Proc Amer Assoc Cancer Res.2006,47:100-107
[219]Higashibata Y, Sakuma T, Kawahata H, Fujihara S, Moriyama K, Okada A, Yasui T, Kohri K, Kitamura Y, Nomura S.Identification of promoter regions involved in cell and developmental stage-specific osteopontin expression in bone,kidney,placenta,and mammary gland:an analysis of transgenic mice[J].J Bone Miner Res.2004,19(1):78-88.
[220]Cohen M, Seroussi E, Band M R. SPP1 is a candidate gene for the QTL affecting milk protein concentration on BTA6 in Israeli Holstein. In:Conference Animal Genetics,Japan.2004b,10-15.
[221]Brown L F, Berse B, Van de Water L, Papadopoulos-Sergiou A, Perruzzi C A, Manseau E J, Dvorak H F,Senger D R. Expression and distribution of osteopontin in human tissues:widespread association with luminal epithelial surfaces[J]. Mol Biol Cell.1992,3:1169-1180.
[222]Senger D R, Perruzzi C A, Papadopoulos A, Tenen D G. Purification of a human milk protein closely similar to tumor-secretedM phosphoproteins and osteopontin[J]. Biochim Biophys Acta.1989,996:43-48.
[223]Tuck A B, Hota C, Wilson S M, Chambers A F. Osteopontin-induced migration of human mammary epithelial cells involves activation of EGF receptor and multiple signal transduction pathways [J]. Oncogene. 2003,22:1198-1205.
[224]White S N, Casas E and Allan M F. Evaluation in beef cattle of six deoxyribonucleic acid markers developed for dairy traits reveals an osteopontin polymorphism associated with postweaning growth [J]. J Dairy Sci.2007,85:1-10
[225]Ron M, Kliger D, Feldmesser E, Seroussi E, Ezra E, Weller J I. Multiple quantitative trait locus analysis of bovine chromosome 6 in the Israeli Holstein population by a daughter design[J].Genetics.2001,159:727-735.
[226]Koning Dirk-Jan de. Conflicting candidates for cattle QTLs[J].Trends in Genetics.2006,22(6):301-305
[227]Lillehammer M, Goddard M E, Nilsen H, Sehested E, Hanne Gro Olsen, Sigbjorn L and Meuwissen T H E.Quantitative trait locus-by-environment interaction for milk yield traits on bostaurus autosome 6 [J].Genetics.2008,179:1539-1546
[2]刘荫武,曹斌云.应用奶山羊生产学.轻工业出版社,1990.
[3]向钊,龙火生,杨公社,左福元.牛泌乳性状的QTL研究进展[J].黄牛杂志2002,7(128),39-41
[4]罗军,曹斌云,姚军虎.奶山羊发展现状与产业化前景展望[A].2006中国羊业进展[C].甘肃,兰州：第三届中国羊业发展大会,2006,74-78.
[5]呼格吉乐图,旭日干,王建国.我国山羊业存在问题及对策[J].畜牧兽医杂志,2007,26(1)：66-68.
[6]曹斌云,罗军,姚军虎.我国山羊奶发展战略及前景分析[J].畜牧兽医杂志,2007,26(1)：51-54.
[7]罗军.奶山羊繁育体系建设现状与思路.第五界中国羊业发展大会论文,2008
[8]Swaisgood H E.Review and update of casein chemistry[J]. J Dairy Sci.1993,76(10):3054-3061
[9]Lincoln D T, Waters M J, Breipohl W. Growth hormone receptor expression in the proliferating rat mammary gland [J]. Acta Histochem.1990,40(Suppl):47-49.
[10]Karen Plant, Mario Ikceda and Barlara K Vonderhaar. Role of growth hormone and insulin-like growth factor I in mammary development [J].Endocr.1993,133(4):1843-1848.
[11]Shackleton M,Vaillant F, Simpson K J, Sting J, Smyth G K.Generation of a functional mammary gland from a single stem cell[J]. Nature.2006,1(439)84-88
[12]Stingl J, Eirew P, Ricketson I. Purification and unique properties of mammary epithelial stem cells [J]. Nature.2006,2(439) 993-997
[13]Mark D A and Sandra Z H. Differential Hormonal Regulation and function of progesterone receptor isoforms in normal adult mouse mammary gland [J].Endocrinology.2007,5(148),2290-2300
[14]Capuco A V, Ellis S E, Hale S A. Lactation persistency:insights from mammary cell proliferation studies [J]. J Anim Sci,2003,81:18-31.
[15]Linzell J L and Peaker M. Mechanism of milk secretion [J]. Physiol Rev.1971,51:564-597
[16]Zulak I M and Keenan T W. Citrate accumulation by a Golgi apparatus-rich fraction from lactating bovine mammary gland [J]. Int J Biochem.1983,15:747-750.
[17]Wendrinska A, Addey C V P, Orange P R, Boddy L M, Hendry K A K and Wildy CJ. Effect of a milk fat globule membrane fraction on cultured mouse mammary cells [J]. Biochem Soc Trans.1993,21: 220-225
[18]Smtth-kirwin S M, O'connor D M, Johnston J, Delancye E, Hassink S G and Funanage V L. Leptin expression in human mammary epithelial cells in breast milk [J]. J Clin Endocrinol Metab.1998,83: 1810-1813.
[19]Mather IH and Keenan TW. Origin and secretion of milk lipids[J]. JAMA.1998,3:259-273.
[20]Margaret C N,Thomas B M and Isabel F. Hormonal regulation of mammary differentiation and milk secretion[J]. J Mammary Gland Biol Neoplasia.2002,1(7),49-66
[21]Shyamala G. Progesterone signaling and mammary gland morphogenesis [J]. J Mammary Gland Biol Neoplasia.1999,4:89-104.
[22]Topper Y J and Freeman S.Multiple hormone interactions in the developmental biology of the mammary gland [J]. Physiol Rev.1980 (60),1049-1106
[23]Margaret C N, Thomas B M and Isabel F.Hormonal regulation of mammary differentiation and milk secretion journal of mammary gland[J]. J Mammary Gland Biol Neoplasia.2002,1(7):49-66
[24]Bocchinfuso W P and Korach K S. Mammary gland development and tumorigenesis in estrogen receptor knockout mice [J]. J Mammary Gland Biol Neoplasia.1997,2:323-334.
[25]Capuco A V, Ellis S E, Hale S A. Lactation persistency:insights from mammary cell proliferation studies [J]. J Anim Sci.2003,81:18-31.
[26]Shamay A, Zeelon E, Ghez Z. Inhibition of casein and fat synthesis and alpha lactalbumin secretion by progesterone in explants from bovine lactating mammary glands [J]. J Endocrinol,1987,113:81-88.
[27]Kastner P, Krust A, Turcotte B. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B [J]. EMBO J,1990,9: 1603-1614.
[28]Schams D, Kohlenberg S, Amselgruber W. Expression and localization of estrogen and progesterone receptors in the bovine mammary gland during development, function and involution [J]. J Endocrinol, 2003,177:305-17.
[29]Delbecchi L, Miller N, Prud'homme C, Petitclerc D, Wagner G F and Lacasse P.17β-estradiol reduces milk synthesis and increases stanniocalcin gene expression in the mammary gland of lactating cows[J]. Liv Prod Sci.2005,12(98),57-66
[30]Delbecchi L, Lacasse P. Suppression of estrous cycles in lactating cows has no effect on milk production[J]. J Dairy Sci.2006,89(2):636-639
[31]Knight C H.Overview of prolactin's role in farm animal lactation[J]. Liv Prod Sci.2001,1(70):87-93
[32]Brockman J L, Schuler L A. Prolactin signals via Stat5 and Oct-1 to the proximal cyclin D1 promoter [J]. Mol Cell Endocrinol.2005,3(239):45-53
[33]Keiko M, Jonathan M S, Gilbert H S. Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium [J]. J Cell Biol.2001,4(155):531-542
[34]Boutinaud M and Jammes H. Growth hormone increases Stat5 and Statl expression in lactating goat mammary gland:a specific effect compared to milking frequency [J].Domest Anim Endocrinol.2004,11(27):363-378,
[35]Salama A A K, Such X, Caja G, Rovai M, Casals R, Albanell E.Effects of once versus twice daily milking throughout lactation on milk yield and milk composition in dairy goats[J].J Dairy Sci. 2003,86:1673-1680
[36]Yamaji D, Kimura K, Watanabe A. Bovine hepatocyte growth factor and its receptor c-Met:cDNA cloning and expression analysis in the mammary gland[J].Domest Anim Endocrinol.2006,3(30):239-246
[37]Provost F L, Miyoshi K, Vilotte Jean-Luc, Bierie B.SOCS3 promotes apoptosis of mammary differentiated cells[J]. Biochem Biophys Res Commun.2005,338 (4),1696-1701
[38]Lambe T, Finlay D, Murphy M and Martin F. Differential expression of connexin 43 in mouse mammary cells[J]. Cell Biol Int.2006,5(30):472-479
[39]Akers R M, Ellis S E and Berry S D. Ovarian and IGF-Ⅰ axis control of mammary development in prepubertal heifers [J]. Domest Anim Endocrinol.2005,8(29):259-267
[40]Akers R M.Major Advances associated with hormone and growth factor regulation of mammary growth and lactation in dairy cows[J].J Dairy Sci.2006,89:1222-1234
[41]Sinowatz F, Schams D, Habermann F, Berisha B and Vermehren M.Localization of fibroblast growth factor Ⅰ (acid fibroblast growth factor) and its mRNA in the bovine mammary gland during mammogenesis, lactation and involution[J].Anat Histol Embryol.2006,35(3):202-207
[42]Emmanuelle F, Nora H, John G, Vesa K. Differential expression of TGF-β isoforms during postlactational mammary gland involution[J]. Cell Tissue Res.2000,300:89-95
[43]Plath A, Einspanier R,Peters F, Sinowatz F, Schams D. Expression of transforming growth factors alpha and beta-1 messenger RNA in the bovine mammary gland during different stages of development and lactation[J]. J Endocrinol.1997,155:501-511
[44]Motyl T,Gajkowska B,Wojewodzka U,Wareski P, Rekiel A,Ploszaj T.Expression of apoptosis-related proteins in involuting mammary gland of sow[J]. Comp Biochem Physiol B Biochem Mol Biol.2001,128: 635-646
[45]Wareski P, Motyl T, Ryniewicz Z, Orzechowski A, Gajkowska B,Wojewodzka U, Ploszaj T. Expression of apoptosis related proteins in mammary gland of goat[J]. Small Rumin Res.2001,40:279-289
[46]Wilde C J, Addey C V P, Li P, Fernig D G. Programmed cell death in bovine mammary tissue during lactation and involution[J]. Exp Physiol.1997,82:943-953
[47]Kordon E C, Mcknight R A, Chamelli J, Lothar H, Glenn M, Gilbert H S. Ectopic TGF-β, expression in the secretory mammary epithelium induces early senescence of the epithelial stem cell population[J]. Developmental Biology.1995,168:47-61.
[48]Zarzynska J, Motyl T. Dissimilar effects of LY 294002 and PD 098059 in IGF-I-mediated inhibition of TGF-beta(1) expression and apoptosis in bovine mammary epithelial cells[J]. J Physiol Pharmacol.2005, 56:181-193.
[49]Zhang Y, Proenca R, Maffei M. Positional Cloning of the Mouse Obese Gene and Its Human Homologue [J]. Nature.1994,372:425-432.
[50]Aoki N, Kawamura M, Matsuda T.Lactation-dependent down regulation of leptin production in mouse mammary gland[J].Biochim Biophys Acta.1999,1427:298-306.
[51]Neville M C, Medina D, Monks J. The mammary fat pad[J]. J Mamm Gland Biol and Neoplasia.1998, 3:109-116.
[52]Xin H, Subhash C. Leptin-a growth factor in normal and malignant breast cells and for normal mammary gland development [J]. J Natl Cancer Inst.2002,94:1704-1711.
[53]Fantuzzi G, Faggioni R. Leptin in the regulation of immunity,inflammation and hematopoiesis [J]. J Leukoc Biol.2000,68 (4):437-446.
[54]李萌,李庆章.奶山羊乳腺中瘦素的信号转导通路.中国乳品工业.2008,10(36)：23-26
[55]Wilde C J, Addey C V, Bryson J M, Finch L M, Knight C H, Peaker M.Autocrine regulation of milk secretion[J]. Biochem Soc Symp.1998,63:81-90.
[56]McManaman J L, Margaret C. Mammary physiology and milk secretion[J]. Neville Advanced Drug Delivery Reviews.2003,55:629-641
[57]Mikaelian I, Hovick M, Silva K A, Burzenski L M.Expression of terminal differentiation proteins defines stages of mouse mammary gland development [J].Vet Pathol.2006,1(43):36-49.
[58]Jenness R. Composition and characteristics of goat milk:Review 1968 - 1979[J]. J Dairy Sci.1980,63: 1605-1630.
[59]Saini A L,Gill R S.Goat milk:an attractive alternate[J].Indian Dairyman.1991,42:562 —564.
[60]Peaker M. Mechanism of milk secretion:milk composition in relation to potential difference across the mammary epithelium [J] J Physiol.1977,270:489-505
[61]Jolivet G, Meusnier C, Chaumaz G. Extracellular matrix regulates alpha sl-casein gene expression in rabbit primary mammary cells and CCAAT enhancer binding protein (C/EBP) binding activity [J]. J Cell Biochem,2001,82(3):371-86.
[62]Kuo C B, Wu W, Xu X. Pseudophosphorylated prolactin (S179D PRL) inhibits growth and promotes beta-casein gene expression in the rat mammary gland [J]. Cell Tissue Res,2002,309(3):429-437,
[63]Yamashita H, Nevalainen M T, Xu J. Role of serine phosphorylation of Stat5a in prolactin-stimulated beta-casein gene expression [J]. Mol Cell Endocrinol,2001,183(1-2):151-163.
[64]Masson P L and Heremans J F. Lactoferrin in milk from different species [J]. Comp Biochem Physiol B.1971,39(1):119-129
[65]Baker E N, Anderson B F, Baker H M, Day C L, Haridas M, Norris G E, Rumball S V, Smith C A and Thomas D H.Three-dimensional structure of lactoferrin in various functional states[J]. Adv Exp Med Biol.1994,1(357):1-12.
[66]Masson P L, Heremans J F and Schonne E. Lactoferrin, an iron-binbing protein nineutrophilic leukocytes[J] J Exp Med.1969,9(130):643-658.
[67]Cramer E, Pryzwansky K B, Villeval J L, Testa U and Breton-Gorius J. Ultrastructural localization of lactoferrin and myeloperoxidase in human neutrophils by immunogold[J]. Blood.1985,65:423-432.
[68]Otto B R, AM Verweij-van Vught and MacLaren D M. Transferrins and heme-compounds as iron sources for pathogenic bacteria [J], Crit Rev Microbiol.1992,18(3):217-33.
[69]Goodman R E and Schanbacher F L. Bovine lactoferrin mRNA:sequence, analysis, and expression in the mammary gland [J].Biochem Biophys Res Commun.1991,180(1):75-84.
[70]Reichenstein M, German T, Barash I. BLG-el-A novel regulatory element in the distal region of the β-lactoglobulin gene promoter[J].FEBS Letters.2005,10 (579) 2097-2104
[71]Moioli B, Napolitano F, Orru L, Catillo G Single nucleotide polymorphism detection in promoter III of the acetyl-CoA carboxylase-alpha gene in sheep[J].J Anim Breed Genet.2005,122(6):418-20.
[72]Hanigan M D, Cant J P, Weakley D C and Beckett J L. An evaluation of postabsorptive protein and amino acid metabolism in the lactating dairy cow [J]. J Dairy Sci.1998,81 (12):3385-3401。
[73]Peel C J, Taylor J W. Robinson I B and Hooley R D.The use of oestrogen, progesterone and reserpine in the artificial induction of lactation in cattle[J].Aust J Biol Sci.1979,32 (2):251-259.
[74]Davis S R, Collier R J, McNamara J P, Head H H and Sussman W. Effects of thyroxine and growth hormone treatment of dairy cows on milk yield, cardiac output and mammary blood flow [J]. J Anim Sci.1988,66:70-79.
[75]Bremmer D R, Overton T R and Clark J H.Production and composition of milk from jersey cows administered bovine somatotropin and fed ruminally protected amino acids[J]J Dairy Sci.1997,80:1374-1380.
[76]Mcguire M A, Griinari J M, Dwyer D A and Bauman D E. Role of insulin in the regulation of mammary synthesis of fat and protein[J] J Dairy Sci.1995,78:816-824.
[77]Griinari J M, McGuire M A, Dwyer D A, Bauman D E and Palmquist D L. Role of insulin in the regulation of milk fat synthesis in dairy cows[J]J Dairy Sci.1997,80:1076-1084.
[78]Griinari J M, Mcguire M A, Dwyer D A, Bauman D E, Barbano D M and House W A. The role of insulin in the regulation of milk protein synthesis in dairy cows[J].J Dairy Sci.1997,80 (10):2361-2371
[79]Moioli B, Pilla F and Tripaldi C. Detection of milk protein genetic polymorphisms in order to improve dairy traits in sheep and goats:a review[J]. Small Rumin Res.1998,3(27):185-195
[80]Dinesh K, Neelam G, Ahlawat S P S, Satyanarayana R,Shyam Sunder, Gupta S C.Single strand confirmation polymorphism (SSCP) detection in exon I of the a-lactalbumin gene of Indian Jamunapari milk goats (Capra hircus)[J]. Genet Mol Biol.2006,2(28):287-293
[81]Martin P, Szymanowska M, Zwierzchowski L, Christine L,Eroux C.The impact of genetic polymorphisms on the protein composition of ruminant milks [J]. Reprod Nutr Dev.2002,42(5):433-459
[82]陈宏,蓝贤勇,李瑞彪,雷初朝,孙维斌,张润锋,郑元林,朱必才CSN1S2、 CSN3和β-1g基因对西农萨能奶山羊产奶性能的影响.遗传学报.2005,32(8)：804-810
[83]Robinson G W, McKnight R A, Smith G H. Mammary epithelial cells undergo secretory differentiation in cycling virgins but require pregnancy for the establishment of terminal differentiation.Development[J].1995,121:2079-2090
[84]Chilliard Y, Ferlay A, Rouel J and Lamberet G. A review of nutritional and physiological factors affecting goat milk lipid synthesis and lipolysis[J]. J Dairy Sci.2003,86:1751-1770
[85]Parodi P W.Conjugated linoleic acid and other anticarcinogenic agents of bovine milk fat[J]. J Dairy Sci.1999,82:1339-1349
[86]Sebedio J L, Gnaedig S and Chardigny J M. Recent advances in conjugated linoleic acid research[J]. Curr Opin Clin Nutr Metab Care.1999,2:499-506.
[87]Williams C M. Dietary fatty acids and human health [J]. Ann Zootech.2000,49:165-180
[88]Sanz Sampelayo M R, Chilliard Y, Schmidely Ph and Boza J. Influence of type of diet on the fat constituents of goat and sheep milk [J]. Small Rumin Res.2007,3(68) 42-63
[89]Reh W A, Maga E A, Collette N M B, Moyer A. Using a Stearoyl-CoA desaturase transgene to alter milk fatty acid composition [J]. J Dairy Sci.2004,87:3510-3514
[90]Liang P, Pardee A B. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction [J]. Science.1992,257(14):967-971
[91]Hubankm, Schatz D G. Identifying differences in mRNA expression by resentational difference analysis of cDNA [J]. Nucleic Acids Res.1994,22:5640-5648
[92]Diatchenko L, Lukyanov S, Lau Y F. Suppression subtractive hybridization:a versatile method for identifying differentially expressed genes [J]. Methods Enzymol.1996,303:349-380.
[93]Yang G P, Ross D T. Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes[J].Nucleic Acids Res.1999,27:1517-1523.
[94]邱志鹏,王种.抑制消减杂交及其应用.生物技术通报.2006年增刊246-250
[95]Adams M D, Kelley J M, Gocayne J D, Dubnick M, Polymeropoulos M H, Xiao H, Merril C R, Wu A, Olde B, Moreno R F. Complementary DNA sequencing expressed sequence tags and human genome project [J].Science.1991,252(5013):1651-1656
[96]Schena M, Shalon D, Davis R W, Brown P O.Quantitative monitoring of gene expression patterns with a complementary DNA microarray[J]. Science.1995,270:467-470
[97]Schulze A. From membranes to chips—a pocket guide to DNA microarray technology:DNA microarrays:gene expression applications [J]. J Cell Sci.2002,115:1781-1785
[98]Veluculescu V E, Zhang L, Vogestein B, Kinzler K W.Serial analysis of gene expression [J]. Science.1995,270:484-487
[99]Ishii M, Hashimoto S, Tsutsumi S, Wada Y, Matsushima K, Kodama T, Aburatani H. Direct comparison of gene chip and SAGE on the quantitative accuracy in transcript profiling analysis [J]. Genomics.2000,68:136-143
[100]Andrade M A, Sander C. Bioinformatics:from genome data to biological knowledge[J].Curr Opin Biotechnol.1997,8:675-683.
[101]Luscombe N M, Greenbaum D, Gerstein M. What is bioinformatics? A proposed definition and overview of the field[J]. Methods Inf Med.2001,40:346-358.
[102]Bonetta L. Bioinformatics-from genes to pathways[J]. Nat Methods.2004,1:169-176.
[103]Bichet A, Polverari D, Malpertuy A. Gene regulation and bioinformatics[J]. Bull Cancer.2005,92: 97-107.
[104]蒋彦,王小行,曹毅等.基础生物信息学及应用[M].北京：清华大学出版社,2003.
[105]王亚辉.世纪之交生物学发展的主要趋势[J].中国科学基金,2000,(3)：167-168
[106]张春霆.生物信息学的现状与展望[J].世界科技研究与发展,2000,(6)：17-20
[107]Amand K B, Terrance E M. Evolutionary analysis by whole genome comparisons [J]. J Bacteriol.2002, (8):2260-2272
[108]Andrada M A,Sander C.Bioinformatics from genome data to biological knowledge[J]. Current Opinion Biotechnol.1997, (6):675-683
[109]Persson B. Bioinformatics in protein analysis [J]. EXS.2000,(88):215-231
[110]da Silveira N J, Uchoa H B, Canduri F, Pereira J H, Camera J C J, Basso L A, Palma M S, Santos D S, de Azevedo W.J.Structural bioinformatics study of PNP from Schistosoma mansoni [J].Biochem Biophys Res Commun.2004, (1):100-104
[111]Geourjon C and Deleage G, SOPMA:significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments[J]. Comput Appl Biosci.1995,11 (6):681-684
[112]Papin J,Subramaniam S.Bioinformatics and cellular signaling[J].Curr Opin Biotechnol.2004,(1):78-81
[113]廖问陶,赵志伟,王茂林.诸葛菜(Orychophragmus violaceus)Toc33基因编码区的克隆及序列分析.四川大学学报(自然科学版),2003,40(1)：163-167.
[114]Raghothama C, Harsha H C, Prasad C K, Pandey A. Bioinformatics and proteomics approaches for aging research[J].Biogerontology.2005,6:227-232
[115]Read T D, Salzberg S L, Pop M, Shumway M, Umayam L, Jiang L, Holtzapple E, Busch J D, Smith K L, Schupp J M, Solomon D, Keim P, Fraser C M. Comparative genome sequencing for discovery of novel polymorphisms in Bacillus anthracis[J].Science,2002,296(5575):2028-2033
[116]Andreas D.Baxevanis, Francis Ouellette B F著,李衍达,孙之荣等译.生物信息学,北京：清华大学出版社,2000
[117]Laurent P, Elduque C, Hayes H, Saunier K, Eggen A and Leveziel H. Assignment of 60 human ESTs in cattle[J]. Mamm Genome.2000,11 (9):748-754
[118]Adams M D, Kelley J M, Gocayne J D, Dubnick M, Polymeropoulos M H, Xiao H, Merril C R,Wu A, Olde B, Moreno R F. Complementary DNA sequencing:expressed sequence tags and human genome project[J]. Science.1991,252:1651-1656
[119]Smith E, Shi L, Drummond P, Rodriguez L, Hamilton R, Powell E, Nahashon S, Ramlal S, Smith G, Foster J. Development and characterization of expressed sequence tags for the turkey (Meleagris gallopavo) genome and comparative sequence analysis with other birds [J]. Anim Genet.2000,31:62-67
[120]Millar A H, Whelan J, Small I.Recent surprises in protein targeting to mitochondria and plastids[J]. Curr Opin Plant Biol.2006,9:610-615
[121]Houdebine LM. Transgenic animal bioreactors [J]. Transgenic Res,2000,9(45),305-320
[122]Bionaz M and Loor J J. Identification of reference genes for quantitative real-time PCR in the bovine mammary gland during the lactation cycle [J]. Physiol Genomics.2007,5(29):312-319.
[123]Holland M S and Holland R E.The cellular perspective on mammary gland development: stem/progenitor cells and beyond [J]. J Dairy Sci.2005,88:E1-E8.
[124]Capuco A V, Wood D L, Baldwin R. Mammary cell number, proliferation and apoptosis during a bovine lactation:relation to milk production and effect of bST[J]. J Dairy Sci.2001a,84:2177-2187.
[125]Livak K J and Schmittgen T D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method[J]. Methods.2001,25:402-408
[126]黄涛,熊远著,徐德全,邓昌彦,雷明刚,蒋思文,郑嵘,姜勋平,李凤娥,李家连,左波.大梅与梅山猪背最长肌正反消减文库的构建及序列分析[J].农业生物技术学报.2006,14(4)：456-461.
[127]曹随忠,李宏滨,王爱华,赵兴绪,杜立新.抑制性消减杂交(SSH)构建乳房炎奶牛外周血白细胞差异表达cDNA文库[J].畜牧兽医学报.2005,36(6)：526-530.
[128]Jenness R. Biochemical and nutritional aspects of milk and colostrum.1985:The Iowa State University Press.164-197.
[129]Ferranti P, Malorni A, Nitti GPrimary structure of ovine alpha sl-caseins:localization of phosphorylation sites and characterization of genetic variants A, C and D[J]. J Dairy Res.1995, 62(2):281-296.
[130]Martin P, Szymanow S M, Zwierzchow S L, Christine L,Eroux C.The impact of genetic po lymorphisms on the prote in composition of ruminant milks[J]. Rep rod Nutr Dev,2002,42 (5):433-459.
[131]Yahyaoui M H, Ang iolillo A, Pilla F, Sanche Z A, Folch J.Characterization and genotyping of the caprine K2casin variantsfJ]. J Dairy Sci,2003,86:2715-2720.
[132]Mackinlay A G W. Milk Proteins, Chemistry and Molecular Biology.1971, New York:Academic Press.172-215.
[133]Shekar P C, Goel S, Rani S D.kappa-casein-deficient mice fail to lactate[J].Proc Natl Acad Sci USA.2006,103(21):8000-8005.
[134]Chanat E, Martin P, Ollivier-Bousquet M. Alpha(Sl)-casein is required for the efficient transport of beta-and kappa-casein from the endoplasmic reticulum to the Golgi apparatus of mammary epithelial cells[J]. J Cell Sci.1999,112:3399-3412.
[135]Svensson M, Hakansson A, Mossberg A K.Conversion of alpha-lactalbumin to a protein inducing apoptosis[J]. Proc Natl Acad Sci USA.2000,97(8):4221-4226.
[136]Kuss A W, Gogo 1 J. Geidermann H.Associations of a polymorphic AP 22 binding site in the 5'flanking region of the bovine beta-lactoglobul in gene with milk proteins[J]. J Dairy Sci,2003,86 (6): 2213-2218.
[137]Jenness R. Biochemical and nutritional aspects of milk and colostrum.1985:The Iowa State University Press.164-197.
[138]Ferranti P, Carbone V, Sannolo N, Fiume I, Malorni A. Mass spectrometric analysis of rat hemoglobin by FAB-overlapping. Primary structure of the alpha-major and of four beta constitutive chains. Int J Biochem.1993,25(12):1943-1950
[139]Jessica Harris, Prudence M. Stanford, Kate Sutherland, Samantha R. Oakes, Matthew J. Naylor, Fiona G. Robertson, Katrina D. Blazek, Michael Kazlauskas, Heidi N. Hilton, Sergio Wittlin, Warren S lexander, Geoffrey J Lindeman, Jane E.Visvader, and Christopher J. Ormandy.Socs2 and Elf5 Mediate Prolactin-Induced Mammary Gland Development[J].Mol Endocrinol.2006,20(5):1177-1187
[140]Zhou J, Chehab R, Tkalcevic J, Naylor M J, Harris J,Wilson T J, Tsao S, Tellis I, Zavarsek S, Xu D, Lapinskas E J, Visvader J, Lindeman G J, Thomas R, Ormandy C J,Hertzog P J, Kola I, Pritchard M A. Elf5 is essential for early embryogenesis and mammary gland development during pregnancy and lactation[J]. EMBO J.2005,24:635-644
[141]Tadashi Y, Shinji N, Hiroshi K.Ghitm is an ortholog of the Bombyx mori prothoracic gland-derived receptor (Pgdr) that is ubiquitously expressed in mammalian cells and requires an N-terminal signal sequence for expression[J]. Biochem Biophys Res Commun.2006,341:13-18
[142]Kerstin R, Claudia Y C, Vesna B, Peter M V.The Growth-hormone inducible transmembrane protein (Ghitm) belongs to the Bax inhibitory protein-like family[J]. Int J Biol Sci.2007,3(7):471-476
[143]Kayla J. Bayless, George E. Davis and Gerald A. Meininger. Isolation and biological properties of osteopontin from bovine milk[J]. Protein Expr Purif.1997,9:309-314.
[144]Leonard S, Khatib H, Schutzkus V. Effects of the osteopontin gene variants on milk production traits in dairy cattle[J]. J Dairy Sci.2005,88:4083-086.
[145]Takehiro Ogata,Tomomi Ueyama,Tetsuya Nomura.Osteopontin is a myosphere-derived secretory molecule that promotes angiogenic progenitor cell proliferation through the phosphoinositide 3-kinase/Akt pathway[J]. Biochem Biophys Res Commun.2007,359:341-347.
[146]Gao Chengjiang, Mi Zhiyong, Guo Hongtao.Osteopontin regulates ubiquitin-dependent degradation of statl in murine mammary epithelial tumor cells[J]. Neoplasia.2007,9(9):699-706.
[147]Nemir M, Bhattacharyya D, Li Xiaoming.Targeted inhibition of osteopontin expression in the mammary gland causes abnormal orphogenesis and lactation deficiency[J].J Biol Chem.2000,275(2):969-976.
[148]Sorensen E S, Hojrup P and Petersen T E.Posttranslational modifications of bovine osteopontin: Identification of twenty-eight phosphorylation and three O-glycosylation sites[J]. Protein Sci. 1995,4:2040-2049.
[149]Albig W, BramLage B,Gruber K, Klobeck Hans-Gustav, Kunz J R and Doenecke D.The Human replacement histone H3.3B gene (H3F3B)[J].Genomics.1995,30:264-272
[150]Yang Y, Spitzer E, Kenney N, Zschiesche W, Li M, Kromminga A, Miiller T, Spener F, Lezius A, Veerkamp J H.Members of the fatty acid binding protein family are differentiation factors for the mammary gland[J].J Cell Biol.1994,127(4):1097-109.
[151]Binas B, Spitzer E, Zschiesche W, Erdmann B, Kurtz A, Mueller T, Niemann C, Blenau W, Grosse R Hormonal induction of functional differentiation and mammary derived growth inhibitor expression in cultured mouse mammary gland explants[J]. In Vitro Cell Dev Biol.1992,28:625-634
[152]Heuckeroth R O, Birkenmeier E H, Levin M S, Gordon J I.Analysis of the tissue-specific expression, developmental regulation, and linkage relationships of a rodent gene encoding heart fatty acid binding protein[J].J Biol Chem.1987,262:9709-9717
[153]Puigserver P, Spiegelman B M. Peroxisome proliferators activated receptor-gamma coactivator 1 alpha (PGC-lalpha):Transcriptional coactivator and metabolic regulator [J]. Endocrinol Rev.2003,24(1), 78-90.
[154]Zhang Q, Boichard D, Hoeschele I, Ernst C, Eggen A, Murkve B, Pfister-Genskow M,Witte L A, Grignola F E, Uimari P, Thaller G, Bishop M D.Mapping quantitative trait loci for milk production and health of dairy cattle in a large outbred pedigree[J]. Genetics.1998,149:1959-1973.
[155]Knutti D,Kralli A.PGC-1:a versatile coactivator [J].Trends Endocrinol and Metab.2001,12(8), 360-365.
[156]Urieli-Shoval S, Linke R P, Matzner Y. Expression and function of serum amyloid A, a major acute phase protein, in normal and disease states [J]. Curr Opin Hematol.2000,7:64-69.
[157]朱大龙,童国玉.血清淀粉样蛋白A-联系肥胖及其代谢合并症的促炎性脂肪细胞因子[J].国际代谢杂志,2006,26(3)：205-210
[158]Pruzanski W, de Beer F C, de Beer M C. Serum amyloid A protein enhances the activity of secretory non-pancreatic phospholipase A2[J]. J Biochem.1995,309:461-464.
[159]Preciado Patt L, Hershkoviz R, Fridkin M. Serum amyloid A binds specific extracellular matrix glycoproteins and induces the adhesion of resting CD4+T cells [J]. J Immunol.1996,156:1189-1195.
[160]Ancsin J B, Kisilevsky R. Characterization of high affinity binding between laminin and the acute-phase protein, serum amyloid A [J]. J Biol Chem.1997,272:406-413.
[161]Baranova I N, Vishnyakova T G, Bocharov A V. Serum amyloid a binding to CLA-1 (CD36 and L IMPII analogous-1) mediates serum amyloid a protein induced activation of ERK1/2 and p38 mitogen-activated protein kinases [J]. J Biol Chem.2005,280:8031-8040.
[162]Casero R A Jr, Pegg A E. Spermidine/spermine N1-acetyltransferase the turning point in polyamine metabolism[J]. FASEB J.1993,7:653-661.
[163]Schluter K D, Frischkopf K, Flesch M. Central role for ornithine decarboxylase in β-adrenoceptor mediated hypertrophy[J].Cardiovasc Res.2000,45(2):410-417.
[164]Kremzner L T. Metabolism of polyamines in the nervous system[J]. Fed Proc.1970,29:1583-1588.
[165]Seiler N,Bolkenius F N.Polyamine reutilization and turnover in brain[J].Neurochem Res. 1985,10:529-544.
[166]Vujcic S, Halmekyto M, Diegelman P, Gan G, Kramer D L, Janne J and Porter C W.Effects of Conditional Overexpression of Spermidine/Spermine N1-Acetyltransferase on Polyamine Pool Dynamics, Cell Growth,and Sensitivity to Polyamine Analogs. J Biol Chem.2000,275(49)38319-38328,
[167]Thomas T, Thomas T J. Polyamines in cell growth and cell death:molecular mechanisms and therapeutic applications [J]. Cell Mol Life Sci.2001,58:244-258.
[168]Babu G N, Sailor K A, Sun D. Spermidine/spermine N1-acetyl transferase activity in rat brain following transient focal cerebral ischemia and reperfusion [J]. Neurosci Lett.2001,300(1):17-20.
[169]Brekken R A, Sage E H. SPARC, a matricellular protein:at the crossroads of cell matrix[J]. Matrix Biol.2000,19(7):569-580.
[170]Francki A, Motamed K, McClure T D. SPARC regulates cell cycle progression in mesangial cells via its inhibition of IGF dependent signaling [J]. J Cell Biochem.2003,88(4):802-811.
[171]Zhou X, Tan F K, Guo X. Small interfering RNA inhibition of SPARC attenuates the profibrotic effect of transforming growth factor betal incultured normal human fibroblasts[J].Arthritis Rheum.2005,52 (1):257-261.
[172]Tadashi U, Kazuhiro S, Tetsuo K, Ikuya Y and Shigekazu N.Molecular cloning and characterization of the chromosomal gene for human lactoperoxidase[J].Eur J Biochem.1997,243,32-41
[173]Lesk AM. Introduction to Bioinformatics [M].1st ed. New York:Oxford University Press.2002, 1-61.
[174]冯浩咏,苗向阳,罗绪刚,胡婕.生物信息学在发现新基因方面的应用.生物技术学报.2007,5：1-5
[175]唐旭清,朱平.后基因组时代生物信息学的发展趋势.生物信息学.2007,3：142-144
[176]Elisabeth G, Alexandre G, Christine H. ExPASy:the proteomics server for in-depth protein knowledge and analysis[J]. Nucleic Acids Res.2003,31(13):3784-3788
[177]成军,刘妍,陆荫英.生物信息学技术与新基因的研究[J].世界华人消化杂志,2003,11(4)：474-4771
[178]Wu Zhidan, Puigserver P, Andersson U, Adelmant G,Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC,Spiegelman B M. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1[J].Cell.1999,98(1):115-124.
[179]Morgan A, Burgoyne R D, Barclay J W. Regulation of exocytosis by protein kinase C[J]. Biochem Soc Trans.2005,33:1341-1344.
[180]Fields S, Song O. A novel genetic system to detect protein-protein interactions [J]. Nature.1989,340: 245-246
[181]Yamane K, Kinsella T J. Casein kinase 2 regulates both apoptosis and the cell cycle following DNA damage induced by 6-thioguanine [J]. Clin Cancer Res.2005,11:2355-2363.
[182]Sodek J, Ganss B, McKee M D.Osteopontin[J].Crit Rev Oral Biol Med.2000,11(3):279-303.
[183]Oldberg A, Franzen A, Heinegard D.Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence[J]. Proc Natl Acad Sci USA.1986,83: 8819-8823.
[184]Colombo S,Longhi R,Alcaro S.N-myristoylation determines dual targeting of mammalian NADH-cytochrome b5 reductase to ER and mitochondrial outermembranes by a mechanism of kinetic partitioning [J]. J Cell Biol.2005,168:735-745.
[185]Quinn P R O, Knabe D A and Wu G. Arginine catabolism in lactating porcine mammary tissue[J]. J Anim Sci.2002,80:467-474
[186]陈英剑,胡成进,赵苗青SYBR Green实时荧光定量PCR技术平台的建立.实用医药杂志,2004,21(11)：997-999.
[187]Overbergh L, Giulietti A, Valckx D. The use of real-time reverse transcriptase PCR for the quantification of cytokine gene expression[J]. J Biomol Tech.2003,14:33-43.
[188]Jain M, Nijhawan A, Tyagi A K, Khurana JP. Validation of housekeep ing genes as internal control for studying gene expression in rice by quantitative real-time PCR [J]. Biochem Biophy Res Commun.2006, 345:646-651.
[189]Wu G Q, Deng X M, Li J Y, Li N, Yang N. A potential molecular marker for selection against abdominal fatness in chickens[J]. Poult Sci.2006,85:1896-1899.
[190]Wiener P, Maclean I, Williams J L,Woolliams J A.Testing for the presence of previously identified QTL for milk production traits in new populations [J]. Anim Genet.2000,31:385-395.
[191]Weikard R, Kuhn C, Goldammer T, Freyer G, Schwerin M.The bovine PPARGC1A gene:Molecular characterization and association of an SNP with variation of milk fat synthesis [J]. Physiol Genomics. 2005,21:1-13.
[192]Georges M, Nielsen D, Mackinnon M, Mishra A, Okimoto R, Pasquino A T, Sargeant L S,Sorensen A,Steele M R, Zhao X, Womack J E, Hoeschele I. Mapping quantitative trait loci controlling milk production in dairy cattle by exploiting progeny testing[J].Genetics.1995,139:907-920.
[193]Freyer G, Sorensen P, Kuhn C, Weikard R, Hoeschele I.Search for pleiotropic QTL on chromosome BTA6 affecting yield traits of milk production[J]. J Dairy Sci.2003,86:999-1008.
[194]Bionaz M, Loor J J. Gene networks driving bovine milk fat synthesis during the lactation cycle[J].BMC Genomics.2008,9(1),366-423.
[195]Khatib H, Zaitoun I, Wiebelhaus-Finger J, Chang Y M, Rosa G J. The association of bovine PPARGC1A and OPN genes with milk composition in two independent Holstein cattle populations [J]. J Dairy Sci.2007,90 (6),2966-2970.
[196]Weikard R, Kuhn C, Goldammer T, Freyer G, Schwerin M. PPARGC1A a candidate gene for a QTL on BTA6 affecting milk fat synthesis.29th Int. Conf. Ani. Gen, ISAG,2004,60pp.
[197]Lin J, Yang R, Tarr P T. Hyperlipidemic effects of dietary saturated fats mediated through PGC-lbeta coactivation of SREBP[J]. Cell.2005,120:261-27
[198]Inman C K,Shore P.The osteoblast transcription factor Run-2 is expressed in mammary epithelial cells and mediates osteopontin expression[J]. J Biol Chem.2003,278(49):48684-48689.
[199]Bayless K J, Davis G E, Meininger G A. Isolation and biological properties of osteopontin from bovine milk[J]. Protein Expr Purif.1997,9:309-314.
[200]Miri C Z, Seroussi E, Larkin D M, Loor J J, Wind A E, Lee J H, Drackley J K, Band M R, Hernandez A G, Shani M, Lewin H A, Weller J I and Ron M. Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle [J]. Genome Res.2005,15:936-944
[201]Rittling S R and Novick K E. Osteopontin expression in mammary gland development and tumorigenesis[J]. Cell Growth Differ.1997,8(10),1061-1069
[202]Nagatomo T,Ohga S,Takada H, Nomura A, Hikino S, Imura M, Ohshima K and Hara T. Microarray analysis of human milk cells:Persistent high expression of osteopontin during the lactation period[J]. Clin Exp Immunol.2004,138(1):47-53
[203]Schnabel R D, Kim J, Ashwell M S, Sonstegard T S, Van Tassell C P, Connor E E and Taylor J F. Fine-mapping milk production quantitative trait loci on BTA6:Analysis of the bovine osteopontin gene[J]. PNAS.2005,102(19):6896-6901
[204]Cohen-Zinder M, Seroussi E, Larkin D M, Loor J J, Wind A E, Lee J H, Drackley J K, Band M R,Hernandez A G, Shani M, Lewin H A, Weller J I, Ron M.Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle[J].Genome Res.2005,15:936-944.
[205]Olsen H G, Nilsen H, Hayes B, Berg P R, Svendsen M, Lien S, Meuwissen T.Genetic support for a quantitative trait nucleotide in the ABCG2 gene affecting milk composition of dairy cattle[J]. BMC Genet. 2007,21:8-32.
[206]Sage E H, Vemon R, Decker J, Funk S, Iruela-Arispe M. Distribution of the calcium-binding protein SPARC in tissues of embryonic and adult mice[J]. J Histochem Cytochem 1989,37:819-834
[207]Peggy L P, E. Helene S, Timothy E L, Sarah E F and Allen M G. Distribution of SPARC in Normal and Neoplastic Human Tissue'[J]. J Histochem Cytochem.1995,8(43):791-800.
[208]Bauman D E, Everett R W,Weiland W H. Production responses to bovine somatotropin in northeast dairy herds [J]. J Dairy Sci.1999,82:2564-2573.
[209]Van Amburgh M E, Galton D M. Management and economics of extended calving intervals with use of bovine somatotropin [J]. Livest Prod Sci.1997,50:15-28.
[210]Knight C H, Fowler P A and Wilde C J. Galactopoietic and mammogenic effects of long-term treatment with bovine growth hormone and thrice daily milking in goats [J]. J Endocrinol.1990,127: 129-138.
[211]Capuco A V, Wood D L, Baldwin R. Mammary cell number, proliferation and apoptosis during a bovine lactation:relation to milk production and effect of bST[J]. J Dairy Sci.2001a,84:2177-2187.
[212]Singh K, Davis S R, Dobson J M, Molenaar A J, Wheeler T T, Prosser C G, Fair V C, Oden K, Swanson K M, Phyn C V C, Hyndman D L, Wilson T, Henderson H V and Stelwagen .K.cDNA microarray analysis reveals that antioxidant and immune genes are upregulated during involution of the bovine mammary gland [J]. J Dairy Sci.2008,91(6):2236-2246
[213]Anthony E Pegg.Spermidine/spermine-N-acetyltransferase:a key metabolic regulator[J].Am J Physiol Endocrinol Metab.2008,294:E995-E1010
[214]司徒镇强,吴军正.细胞培养[M].西安：世界图书出版社,2006
[215]杨芳,路国华,刘利兵,刘芳娥,曲萍.影响MTT比色试验的关键环节.第四军医大学学报.2009,30 (3)：243-247
[216]Sharp J A, Sung V, Slavin J, Thompson E W, Henderson M A.Tumor cells are the source of osteopontin and bone sialoprotein expression in human breast cancer[J]. Lab Invest.1999,79(7):869-877.
[217]Das Riku, Mahabeleshwar G H, Kundu G C.Osteopontin stimulates cell motility and nuclear factor B-mediated secretion of urokinase type plasminogen activator through phosphatidylinositol 3-kinase/akt signaling pathways in breast cancer cells[J]. J Biol Chem.2003,31(278):28593-28606.
[218]Laura K. Sickafoose, Qian J. Chen, Meghan B. Wood, Robert D. Cardiff, Jeffrey P. Gregg and Alexander D B. Osteopontin overexpression in the mouse mammary epithelium induces proliferation and potentates mammary carcinogenesis[J].Proc Amer Assoc Cancer Res.2006,47:100-107
[219]Higashibata Y, Sakuma T, Kawahata H, Fujihara S, Moriyama K, Okada A, Yasui T, Kohri K, Kitamura Y, Nomura S.Identification of promoter regions involved in cell and developmental stage-specific osteopontin expression in bone,kidney,placenta,and mammary gland:an analysis of transgenic mice[J].J Bone Miner Res.2004,19(1):78-88.
[220]Cohen M, Seroussi E, Band M R. SPP1 is a candidate gene for the QTL affecting milk protein concentration on BTA6 in Israeli Holstein. In:Conference Animal Genetics,Japan.2004b,10-15.
[221]Brown L F, Berse B, Van de Water L, Papadopoulos-Sergiou A, Perruzzi C A, Manseau E J, Dvorak H F,Senger D R. Expression and distribution of osteopontin in human tissues:widespread association with luminal epithelial surfaces[J]. Mol Biol Cell.1992,3:1169-1180.
[222]Senger D R, Perruzzi C A, Papadopoulos A, Tenen D G. Purification of a human milk protein closely similar to tumor-secretedM phosphoproteins and osteopontin[J]. Biochim Biophys Acta.1989,996:43-48.
[223]Tuck A B, Hota C, Wilson S M, Chambers A F. Osteopontin-induced migration of human mammary epithelial cells involves activation of EGF receptor and multiple signal transduction pathways [J]. Oncogene. 2003,22:1198-1205.
[224]White S N, Casas E and Allan M F. Evaluation in beef cattle of six deoxyribonucleic acid markers developed for dairy traits reveals an osteopontin polymorphism associated with postweaning growth [J]. J Dairy Sci.2007,85:1-10
[225]Ron M, Kliger D, Feldmesser E, Seroussi E, Ezra E, Weller J I. Multiple quantitative trait locus analysis of bovine chromosome 6 in the Israeli Holstein population by a daughter design[J].Genetics.2001,159:727-735.
[226]Koning Dirk-Jan de. Conflicting candidates for cattle QTLs[J].Trends in Genetics.2006,22(6):301-305
[227]Lillehammer M, Goddard M E, Nilsen H, Sehested E, Hanne Gro Olsen, Sigbjorn L and Meuwissen T H E.Quantitative trait locus-by-environment interaction for milk yield traits on bostaurus autosome 6 [J].Genetics.2008,179:1539-1546