发育相关基因在新生死亡体细胞克隆牛中的表达
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摘要
尽管体细胞克隆在许多物种中都获得了成功，但克隆效率却非常低，只有低于4％的重组胚胎可以发育成活的个体。若体细胞克隆技术在医药及农业等方面得到广泛应用，必需首先解决克隆效率低的问题。由于供体核支持整个克隆动物的发育，所以当供体核被移入去核的卵母细胞后，必需进行重编程，回到胚胎发育的起始阶段。在重编程过程中，供体核必需正确激活对早期胚胎发育有重要作用的基因，抑制在供体核中表达的、与分化相关的基因。目前认为：供体核的不完全重编程，导致在发育过程中有重要作用的基因没有表达或异常表达，是克隆效率低的主要原因。有关基因在克隆动物中表达的研究目前主要集中在植入前的克隆胚胎中。有一些克隆动物在出生后不久死亡，并表现出某些器官发育异常，但造成克隆动物器官异常和出生死亡的原因并不清楚。应用成纤维细胞进行核移植生产体细胞克隆动物许多优势。首先，从一个有价值的动物中，很容易得到皮肤的活体组织，这样通过体细胞克隆便可以生产大量的、具有相同遗传物质的克隆动物。其次，成纤维细胞很容易培养及冷冻储存，是改变细胞遗传物质从而生产转基因克隆动物很好的材料来源。
本研究应用40日龄荷斯坦奶牛的胎儿成纤维细胞和4岁荷斯坦奶牛的耳组织成纤维细胞作为供体核的来源生产体细胞克隆牛，其囊胚率分别达到了37.9％和27.9％，分别有3.4％(10／294)和3.9％(11／283)的重组胚胎发育到出生个体，这些发育到出生个体的胚胎分别有4头和5头在出生时死亡。对这些克隆牛我们进行了尸检，发现某些克隆牛心脏、肝脏、脾脏、肺脏、肾脏和大脑的发育存在着异常，其中以心脏和肺脏的异常最为严重，分别有7头克隆牛的心脏和肺脏发现异常。我们对克隆牛的组织制作常规石蜡切片进行观察，发现克隆牛的器官在发育过程中存在着严重的病理学变化
为了研究造成克隆动物出生死亡和器官发育异常的可能分子机理，我们用荧光定量RT-PCR技术研究了22个在胚胎发育和器官形成过程中有重要作用的基因在出生死亡的克隆牛心脏、肝脏、脾脏、肺脏、肾脏和大脑等6个组织中的表达，其中包括4个对染色质进行修饰的基因(DNMT、PCAF、MeCP2、EED)、类胰岛素生长因子系统的8个基因(IGF1、IGF2、IGF1R、IGF2R、IGFBP1、IGFBP2、IBGBP3和IGFBP4)、成纤维生长因子(FGF2和FGF10)和成纤维生长因子受体(FGFR1和FGFR2)以及另外6个对发育有重要作用的基因(EGFR、PDGFRa、VEGF、BMP4、Hsp70.1和Xist)。
结果表明：在22个被研究的基因中，有16个在体细胞克隆牛的组织中表达发生异常。其中IGFBP4在体细胞克隆牛的5个组织中表达发生异常：IGF2R和BMP4在体细胞克隆牛的4个组织中表达发生异常；DNMT、PCAF、IGF2、VEGF和Hsp70.1等5个基因在体细胞克隆牛的3个组织中表达发生异常；FGF10、FGFR1和PDGFRa等3个基因在体细胞克隆牛的3个组织中表达发生异常：IGF1R、IGFBP2、IGFBP3、EGFR和Xist等5个基因各在体细胞克隆牛的1个组织中表达发生异常。EED、MECP2、IGF1、IGF1R、FGF2和FGFR2等6个基因在体细
中国农业大学博士学位论文
中文摘要
胞克隆牛的组织中未发现表达异常。
从基因异常表达的器官角度分析，心脏是发现基因异常表达最多的器官，有川个基因在体
细胞克隆牛的心脏中表达发生异常，其中9个表现为显著升高。体细胞克隆牛的肝脏中有7个
基因表达发生异常，其中5个表现为显著升高。体细胞克隆牛的肺脏、’肾脏和大脑中均有6个
基因表达发生异常，其中肾脏中异常表达的6个基因均表现为显著降低，也是6个被研究器官
中唯一的一个基因异常表达的趋势表现为一致的器官。脾脏是6个被研究器官中发现基因异常
表达最少的器官，有4个基因在体细胞克隆牛的脾脏中表达发生。
比较来自两种不同供体细胞的克隆牛之间的表达差异，发现有8个基因(IGFZR、HsP7()l、
Xist、PDGFRa、BMP4、IGFBP4、FGF10及IGFZ)的表达在来自成年成纤维细胞的克隆牛
和来自胎儿成纤维细胞的克隆牛的某个组织中存在显著差异。
在16个异常表达的基因中(只有在一个组织中异常表达的基因除外)，有3个基因在体细
胞克隆牛组织中表现出相同的异常表达趋势。其中VEGF在3个异常表达的组织中均表现为显
著升高，FGFRI在2个异常表达的组织中也均表现为显著升高，而PDGFRa在2个异常表达的
组织中均表现为显著降低。在所有异常表达的状态中(39个)，显著升高的有24个，而显著降
低的有巧个。
由于这些基因在胚胎发育和器官形成过程中有重要作用，所以它们的异常表达可能是造成
克隆动物出生死亡和器官发育异常的原因。
Somatic cloning has been succeeded in some species, but the cloning efficiency is very low, which limits the application of the technique in many areas of research and biotechnology. The cloning of mammals by somatic cell nuclear transfer (NT) requires epigenetic reprogramming of the differentiated state of donor cell to a totipotent, embryonic ground state. Accumulating evidence indicates that incomplete or inappropriate epigenetic reprogramming of donor nuclei is likely to be the primary cause of failures in nuclear transfer. Examination of gene expression in cloned animals has largely been limited to preimplantation embryos for a small number of genes important for early embryogenesis. Cloning by somatic nuclear transfer is an inefficient, process in which some of the cloned animals die shortly after birth and display organ abnormalities. In somatic cloning of cattle, fibroblast was often used as donor nuclear. Fibroblasts offer several advantages for future applications of somatic cloning. First, the ski
n biopsy can be easily gained from a valuable animal, so that to produce large numbers of genetically identical copies of the animal are possible. Secondly, fibroblasts can easily cultured and stored frozen, and which are probably good candidates for genetic modification to produce transgenic animals.
In this research, the donor nuclei were obtained from skin fibroblast cells of a female four-year-old elite Holstein cow and from fetal fibroblast cells of a 40-day-old female fetus. About 27.9% (n=283) and 37.9% (n=294) of reconstructed embryos derived from adult fibroblast cell and from fetal fibroblast respectively developed into blastocysts, with 11(14.9%, n=74) and 10 (22.7%, n=44) of the transferred embryos developing into full-term calves. Six of the eleven calves from adult fibroblast cell survived and remained healthy, and five died. Six often calves from the fetal fibroblast cells survived and remained healthy, while four died. All of the deceased cloned cattle died within 48 hours of birth. The abnormalities were observed at necropsy and tissue pathologic section of deceased cloned cattle' organs, including heart, liver, spleen, lung, kidney and brain, and in which the abnormalities of heart and lung were serious.
In an effort to determine the possible genetic causes of neonatal death and organ abnormalities, we have examined expression patterns of 22 developmentally important genes in six organs (heart, liver, spleen,lung,kidney and brain )of both neonatal death cloned bovines and normal control calves produced by artificial insemination (AI) using real-time quantitative RT-PCR. The genes include four genes of modifying chromatin strcture (DNNT, PCAF, MeCP2, EED) eight genes of insulin-like growth factors systems (IGF1, 1GF2, IGF1R, IGF2R, IGFBP1, IGFBP2, IBGBP3 and IGFBP4)s fibroblast growth factor (FGF2 and FGF10) and fibroblast growth factor receptor (FGFR1 FGFR2 )and other six developmentally important genes( EGFR, PDGFRa, VEGF, BMP4, Hsp70.1 and
Aberrant expressions of sixty genes were found in these clones The aberrant expressions of IGFBP4 were observed in five organs; IGF2R and BMP4 in four organs; five genes of DNMT, PCAF, IGF2, VEGF Hsp70.1 in three organs; three genes of FGF10 FGFR1 and PDGFRa in two organs, and aberrant expressions of five genes ofIGFlR IGFBP2 IGFBP3 EGFR and Xist were only observed in one organs.
For the studied genes, spleen was the organ that less affected by gene dysregulaion in which four genes were aberration, whereas heart was the most affected one, in which ten genes were aberration, in liver, seven genes were aberration and five genes were up-regulation. In lung, kidney and brain, six genes were aberration and kidney was the only organ with all dysregulated genesof down-regulation
Comparing the gene expression between the two types clones with each other and eight gene (IGF2R, Hsp70.1 Xist PDGFRa BMP4 IGFBP4 FGF10 and IGF2) expression were found having significant difference between AF cell-derived and FF cell-derived clones.
For the sixty aberrant e
本研究应用40日龄荷斯坦奶牛的胎儿成纤维细胞和4岁荷斯坦奶牛的耳组织成纤维细胞作为供体核的来源生产体细胞克隆牛，其囊胚率分别达到了37.9％和27.9％，分别有3.4％(10／294)和3.9％(11／283)的重组胚胎发育到出生个体，这些发育到出生个体的胚胎分别有4头和5头在出生时死亡。对这些克隆牛我们进行了尸检，发现某些克隆牛心脏、肝脏、脾脏、肺脏、肾脏和大脑的发育存在着异常，其中以心脏和肺脏的异常最为严重，分别有7头克隆牛的心脏和肺脏发现异常。我们对克隆牛的组织制作常规石蜡切片进行观察，发现克隆牛的器官在发育过程中存在着严重的病理学变化
为了研究造成克隆动物出生死亡和器官发育异常的可能分子机理，我们用荧光定量RT-PCR技术研究了22个在胚胎发育和器官形成过程中有重要作用的基因在出生死亡的克隆牛心脏、肝脏、脾脏、肺脏、肾脏和大脑等6个组织中的表达，其中包括4个对染色质进行修饰的基因(DNMT、PCAF、MeCP2、EED)、类胰岛素生长因子系统的8个基因(IGF1、IGF2、IGF1R、IGF2R、IGFBP1、IGFBP2、IBGBP3和IGFBP4)、成纤维生长因子(FGF2和FGF10)和成纤维生长因子受体(FGFR1和FGFR2)以及另外6个对发育有重要作用的基因(EGFR、PDGFRa、VEGF、BMP4、Hsp70.1和Xist)。
结果表明：在22个被研究的基因中，有16个在体细胞克隆牛的组织中表达发生异常。其中IGFBP4在体细胞克隆牛的5个组织中表达发生异常：IGF2R和BMP4在体细胞克隆牛的4个组织中表达发生异常；DNMT、PCAF、IGF2、VEGF和Hsp70.1等5个基因在体细胞克隆牛的3个组织中表达发生异常；FGF10、FGFR1和PDGFRa等3个基因在体细胞克隆牛的3个组织中表达发生异常：IGF1R、IGFBP2、IGFBP3、EGFR和Xist等5个基因各在体细胞克隆牛的1个组织中表达发生异常。EED、MECP2、IGF1、IGF1R、FGF2和FGFR2等6个基因在体细
中国农业大学博士学位论文
中文摘要
胞克隆牛的组织中未发现表达异常。
从基因异常表达的器官角度分析，心脏是发现基因异常表达最多的器官，有川个基因在体
细胞克隆牛的心脏中表达发生异常，其中9个表现为显著升高。体细胞克隆牛的肝脏中有7个
基因表达发生异常，其中5个表现为显著升高。体细胞克隆牛的肺脏、’肾脏和大脑中均有6个
基因表达发生异常，其中肾脏中异常表达的6个基因均表现为显著降低，也是6个被研究器官
中唯一的一个基因异常表达的趋势表现为一致的器官。脾脏是6个被研究器官中发现基因异常
表达最少的器官，有4个基因在体细胞克隆牛的脾脏中表达发生。
比较来自两种不同供体细胞的克隆牛之间的表达差异，发现有8个基因(IGFZR、HsP7()l、
Xist、PDGFRa、BMP4、IGFBP4、FGF10及IGFZ)的表达在来自成年成纤维细胞的克隆牛
和来自胎儿成纤维细胞的克隆牛的某个组织中存在显著差异。
在16个异常表达的基因中(只有在一个组织中异常表达的基因除外)，有3个基因在体细
胞克隆牛组织中表现出相同的异常表达趋势。其中VEGF在3个异常表达的组织中均表现为显
著升高，FGFRI在2个异常表达的组织中也均表现为显著升高，而PDGFRa在2个异常表达的
组织中均表现为显著降低。在所有异常表达的状态中(39个)，显著升高的有24个，而显著降
低的有巧个。
由于这些基因在胚胎发育和器官形成过程中有重要作用，所以它们的异常表达可能是造成
克隆动物出生死亡和器官发育异常的原因。
Somatic cloning has been succeeded in some species, but the cloning efficiency is very low, which limits the application of the technique in many areas of research and biotechnology. The cloning of mammals by somatic cell nuclear transfer (NT) requires epigenetic reprogramming of the differentiated state of donor cell to a totipotent, embryonic ground state. Accumulating evidence indicates that incomplete or inappropriate epigenetic reprogramming of donor nuclei is likely to be the primary cause of failures in nuclear transfer. Examination of gene expression in cloned animals has largely been limited to preimplantation embryos for a small number of genes important for early embryogenesis. Cloning by somatic nuclear transfer is an inefficient, process in which some of the cloned animals die shortly after birth and display organ abnormalities. In somatic cloning of cattle, fibroblast was often used as donor nuclear. Fibroblasts offer several advantages for future applications of somatic cloning. First, the ski
n biopsy can be easily gained from a valuable animal, so that to produce large numbers of genetically identical copies of the animal are possible. Secondly, fibroblasts can easily cultured and stored frozen, and which are probably good candidates for genetic modification to produce transgenic animals.
In this research, the donor nuclei were obtained from skin fibroblast cells of a female four-year-old elite Holstein cow and from fetal fibroblast cells of a 40-day-old female fetus. About 27.9% (n=283) and 37.9% (n=294) of reconstructed embryos derived from adult fibroblast cell and from fetal fibroblast respectively developed into blastocysts, with 11(14.9%, n=74) and 10 (22.7%, n=44) of the transferred embryos developing into full-term calves. Six of the eleven calves from adult fibroblast cell survived and remained healthy, and five died. Six often calves from the fetal fibroblast cells survived and remained healthy, while four died. All of the deceased cloned cattle died within 48 hours of birth. The abnormalities were observed at necropsy and tissue pathologic section of deceased cloned cattle' organs, including heart, liver, spleen, lung, kidney and brain, and in which the abnormalities of heart and lung were serious.
In an effort to determine the possible genetic causes of neonatal death and organ abnormalities, we have examined expression patterns of 22 developmentally important genes in six organs (heart, liver, spleen,lung,kidney and brain )of both neonatal death cloned bovines and normal control calves produced by artificial insemination (AI) using real-time quantitative RT-PCR. The genes include four genes of modifying chromatin strcture (DNNT, PCAF, MeCP2, EED) eight genes of insulin-like growth factors systems (IGF1, 1GF2, IGF1R, IGF2R, IGFBP1, IGFBP2, IBGBP3 and IGFBP4)s fibroblast growth factor (FGF2 and FGF10) and fibroblast growth factor receptor (FGFR1 FGFR2 )and other six developmentally important genes( EGFR, PDGFRa, VEGF, BMP4, Hsp70.1 and
Aberrant expressions of sixty genes were found in these clones The aberrant expressions of IGFBP4 were observed in five organs; IGF2R and BMP4 in four organs; five genes of DNMT, PCAF, IGF2, VEGF Hsp70.1 in three organs; three genes of FGF10 FGFR1 and PDGFRa in two organs, and aberrant expressions of five genes ofIGFlR IGFBP2 IGFBP3 EGFR and Xist were only observed in one organs.
For the studied genes, spleen was the organ that less affected by gene dysregulaion in which four genes were aberration, whereas heart was the most affected one, in which ten genes were aberration, in liver, seven genes were aberration and five genes were up-regulation. In lung, kidney and brain, six genes were aberration and kidney was the only organ with all dysregulated genesof down-regulation
Comparing the gene expression between the two types clones with each other and eight gene (IGF2R, Hsp70.1 Xist PDGFRa BMP4 IGFBP4 FGF10 and IGF2) expression were found having significant difference between AF cell-derived and FF cell-derived clones.
For the sixty aberrant e
引文
1. Aarskog NK, Vedeler CA. Real-time quantitative polymerase chain reaction. A new method that detects both the peripheral myelin protein 22 duplication in Charcot-Marie-Tooth type 1A disease and the peripheral myelin protein 22 deletion in hereditary nettropathy with liability to pressure palsies. Hum Genet, 2000, 107:494-8
2. Abboud HE. Role of platelet-derived growth factor in renal injury. Annu Rev Physiol, 1995, 57: 297-309
3. Agabiti-Rosei E, Muiesan ML Prognostic significance of left ventricular hypertrophy regression. Adv Exp Med Biol, 1997, 432:199-205
4. Aonymous.Translational research:the role of VEGF intu-morangiogenesis. Proceedings of asymposium. Oncologist, 2000, 5(Supp 11): 1-57
5. Anversa P, Nadal-Ginard B Myocyte renewal and ventricular remodelling Nature, 2002, 415: 240-3
6. Arat S, Rzucidlo SJ, Gibbons J, Miyoshi K, Stice SL. Production of transgenic bovine embryos by transfer of transfected granulosa cells into enucleated oocytes. Mol Reprod Dev, 2001, 60: 20-6
7. Arman E, Haffner-Krausz R, Chen Y, Heath JK, Lonai P. Targeted disruption of fibroblast growth factor(FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development. Proc Natl Acad Sci U S A, I998, 95:5082-7
8. Arman E, Haffner-Krausz R, Gorivodsky M, Lonai P. Fgfr2 is required for limb outgrowth and lung-branching morphogenesis. Proc Natl Aead Sei U S A 1999; 96:11895-11899
9. Baguisi A, Behboodi E, Melican DT, Pollock JS, Destrempes MM, Cammuso C, Williams JL, Nims SD, Porter CA, Midura P, Palaeios MJ, Ayres SL, Denniston RS, Hayes ML, Ziomek CA, Meade HM, Godke RA, Gavin WG, Overstrom EW, Echelard Y. Production of goats by somatic cell nuclear transfer. Nat Biotechnol, 1999, 17:456-461
10. Barlow DP. Genomic imprinting in mammalian. Science, 1995, 270:1610-1613
11. Bauer MK, Harding JE, Bassett NS, Breier BH, Oliver MH, Gallaher BH, Evans PC, Woodall SM, Gluckman PD. Fetal growth and placental function. Mol Cell Endocrinol, 1998, 140:115-120
12. Beeker K, Pan D, Whitely CB. Real-time quantitative polymerase chain reaction to assess gene transfer. Hum Gene Ther, 1999, 10:2559-2566
13. Bellusci S, Henderson R, Winnier G, Oikawa T, Hogan BL. Evidence from normal expression and targeted misexpression that bone morphogenetic protein (Bmp-4) plays a role in mouse embryonic lung morphogenesis. Development, 1996, 122:1693-1702
14. Betts DH, Bordignon V, Hill J K, Winger Q, Westhusin ME, Smith LC, King WA. Reprogramming of telomerase activity and rebuilding of telomere length in cloned cattle. Proc Natl Acad Sci USA, 2001, 98:1077-1082
15. Bieche I, Oondy E Laurendeau I, Olivi M, Vidaud D, Lidereau R, Vidaud M. Real-time reverse transcription-PCR assay for future nagement of ERBB2-based clinical apolications. Clin Chem, 1999, 45:1148-1156
16. Biniszkiewicz D, Gribnau J, Ramsahoye B, Gaudet F, Eggan K, Humpherys D, Mastrangelo M-A, Jun Z, Walter J, Jaenisch R. Dnmtl Overexpression Causes Genomic Hypermethylation, Loss of
Imprinting, and Embryonic Lethality. Molecular and Cellular Biology, 2002, 22:2124-2135
17. Bird AP. Wolffe AP. Methylation-induced repression—belts, braces, and chromatin. Cell. 1999. 99:451-454
18. Bostrom H. Gritli-Linde A, Betsholtz C. PDGF-A/PDGF alpha-receptor signaling is required for lung growth and the formation of alveoli but not for early lung branching morphogenesis. Dev Dvn. 2002, 223:155-162
19. Bourc'his D. Le Bourhis D, Patin D, Niveleau A, Comizzoli E Renard JR Viegas-Pequignot E. Delaved and incomplete reprogramming of chromosome methylation pattenrns in bovine cloned embryos. Curr Biol. 2001, 11:1542-1546
20. Brockdorff N. The role of Xist in X-inactivation. Curr Opin Genet Dev, 1998.8:328-333
21. Brown KW. Villar AJ, Bickmore W, Clayton-Smith J, Catchpoole D, Maher ER, Reik W Imprinting mutation in the Beckwith-Wiedemann syndrome leads to biallelic IGF2 expression through an H19-independent pathway. Hum Mol Genet, 1996, 5:2027-2032
22. Campbell KH, McWhir J, Ritchie WA, Wilmut I. Sheep cloned by nuclear transfer from a cultured cell line Nature, 1996, 380:64-66
23. Cancilla B. Ford-Perriss MD, Bertram JE Expression and localization of fibroblast growth factors and fibroblast growth factor receptors in the developing rat kidney. Kidney Int, 1999, 56: 2025-39.
24. Carlson LL, Page AW, Bestor TH. Properties and localization of DNA methyltransferase in preimplantation mouse embryos: implications for genomic imprinting. Genes Dev, 1992, 6: 2536-2541
25. Carmeliet R Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature, 1996, 380:435-439
26. Cezar GG Bartolomei MS, Forsberg E J, First NL, Bishop MD, Eilertsen KJ. Genome-wide epigenetic alterations in cloned bovine fetuses. Biol Reprod, 2003, 68:1009-1014
27. Chao W. Huynh KD, Spencer RJ, Davidow LS, Lee JT. CTCF, a candidate trans-acting factor for X-inactivation choice. Science, 2002, 295:345-7
28. Chavatte-Palmer P, Heyman Y, Richard C, Monger P, LeBourhis D, Kann G, Chilliard Y, Vignon X, Renard JP. Clinical, hormonal, and hematologic characteristics of bovine calves derived from nuclei from somatic cells. Biol Reprod, 2002, 66:1596-1603
29. Chen Z, Yung WK. A reliabili.ty test of standard-based quantitative PCR: exogenous vs endogenous standards. Mol. Cell Probes. 2000, 14:127-135
30. Chesne P, Adenot PG, Viglietta C, Baratte M, Boulanger L, Renard JP. Cloned rabbits produced by nuclear transfer from adult somatic cells. Nat Biotechnol, 2002, 20:366-369
31. Cibelli JB. Stice SL, Golueke P J, Kane JJ, Jerry J, Blackwell C, Ponce de Leon FA, Robl JM. Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science, 1998, 280: 1256-8
32. Chien KR, Zhu H, Knowlton KU, Miller-Hance W, van-Bilsen M, O'Brien TX, Evans SM. Transcriptional regulation during cardiac growth and development. Annu Rev Physiol, 1993, 55: 77-95
33. Chung YG. Ratnam S, Chaillet JR, Latham KE. Abnormal regulation of DNA methyltransferase expression in cloned mouse embryos. Biol Reprod, 2003, 69:146-153
34. Connolcy DT Vascular permeability factor:aunique regulator of blood vessel function. J Cell Biochem, 1991,47: 219-223
35. Costes B, Girodon E, Vidaud D, Flori E, Ardalan A, Conteville P, Fanen P, Niel F, Vidaud M, Goossens M. Prenatal detection by real-time quantitative PCR and characterization of a new CFTR deletion, 3600+15kbde15.3kb (or CFTRdele19). Clin Chem, 2000, 46:1417-20
36. Counter CM, Avilion AA, LeFeuvre CE, Stewart NG, Greider CW, Harley CB, Bacchetti S. Telomere shortening associated with chromosome instability is arrested in immortal ceils which express telomerase activity. EMBO J, 1992, 11 : 1921-1929
37. Cuevas P, Burgos J, Baird A. Basic fibrobroblast growth factor(FGF) promote scartilege repair in vivo. Biochem Biophys Res Commun, 1988, 156:611-618
38. Daniel TO, Kumjian DA. Platelet-derived growth factor in renal development and disease. Semin Nephrol, 1993, 13:87-95
39. Daniels R, Hall V, Trounson AO. Analysis of gene transcription in bovine nuclear transfer embryos reconstructed with granulosa cell nuclei. Biol Reprod, 2000, 63:1034-1040
40. Daniels R, Hall VJ, French AJ, Korfiatis NA, and Trounson AO. Comparison of gene transcription in cloned bovine embryos produced by different nuclear transfer techniques. Mol Reprod Dev, 2001, 60:281-288
41. Davie JR. Covalent modifications of histones: expression from chromatin templates. Curr Opin Genet Dev, 1998, 8:173-8
42. Davis TL, Yang GJ, McCarrey JR, Bartolomei MS. The H19 methylation impnnt is erased and re-established differentially on the parental alleles during male germ cell development. Hum Mol Genet, 2000, 9:2885-2894
43. Dean W, Santos F, Stojkovic M, Zakhartchenko V, Walter J, Wolf E, Reik W. Conservation of methylation reprogramming in mammalian development: aberrant reprogramming in cloned embryos. Proc Natl Acad Sci U S A, 2001, 98:13734-13738
44. DeChiara TM, Efstratiadis A, and Robertson EJ. A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor Ⅱ gene disrupted by targeting. Nature, 1990, 345: 78-80
45. Delot EC, Bahamonde ME, Zhao M, Lyons KM. BMP signaling is required for septation of the outflow tract of the mammalian heart. Development, 2003, 130: 209-220.
46. Delot EC. Control of endocardial cushion and cardiac valve maturation by BMP signaling pathways. Mol Genet Metab, 2003, 80: 27-35.
47. Deng CX, Wynshaw-Boris A, Shen MM, Daugherty C, Ornitz DM, Leder P. Murine FGFR-1 is required for early postimplantation growth and axial organization. Genes Dev, 1994, 8: 3045-3057.
48. DiFiore JW, Wilson JM. Lung development. Seminars in Pediatric Surgery., 1994, 3:221-32
49. Dor Y, Klewer SE, McDonald JA, Keshet E, Camenisch TD. VEGF modulates early heart valve formation. Anat Rec, 2003, 271A: 202-208
50. Dupont J, Holzenberger M. Biology of insulin-like growth factors in development. Birth Defects Res Part C Embryo Today, 2003, 69:257-71
51. Du Z, Cong H, Yao Z. Identification of putative downstream genes of Oct-4 by suppression-subtractive hybridization. Biochem Biophys Res Commun, 2001,282:701-706
52. Ebendal T, Bengtsson H, Soderstrom S. Bone morphogenetic proteins and their receptors: potential functions in the brain. Neurosci Res, 1998, 51:139-146
53. Egawa C. Mivoshi Y. Takamura Y, Taguchi T, Tamaki Y, Noguchi S. Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancer, Int J Cancer, 2001, 95: 255-9
54. Eggan K. Akutsu H. Hochedlinger K, Rideout W. Yanagimachi R. Jaenisch R..X-Ctu-omosome inactivation in cloned mouse embryos. Science, 2000, 290:1578-1581
55. Enright BP, Jeong BS, Yang X, Tian XC. Epigenetic characteristics of bovine donor cells for nuclear transfer: levels of histone acetylation. Biol Reprod, 2003, 69: 1525-1530
56. Enright BP, Kubota C, Yang X, Tian XC. Epigenetic characteristics and development of embryos cloned from donor cells treated by trichostatin A or 5-aza-2'-deoxytytidine. Biol Reprod, 2003, 69 896-901
57. Ezashi T. Ghosh D, Roberts R M. Repression of Ets-2-induced transactivaton of the tau interferon promoter by Oct-4. Mol Cell Biol, 2001, 21:7883-7891
58. Faragher RG. Kipling D. How might replicative senescence contribute to human aging? Bioessays, 1998, 20:985-991
59. Fei X, Tian XC, Du FL, Kubota C, Taneja-M, Dirnnyes A, Dai YR Levine H, Yang X. Aberrant patterns of X chromosome inactiviation in bovine clones. Nat Geuet, 2002, 31: 216-219.
60. Ferrara N, Henzel WJ .Pituitary follicular cells secrete anove heparin-binding growth factor specific for vascular endothelia cells. Biochem Biophys Res Commun, 1989, 161: 851858.
61. Ferrara N, Carvermoore K, Chen H, Dowd M, Lu L, Oshea KS, Powellbraxton L, Hillan KJ, Moore MW Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature, 1996, 380: 439-442.
62. Ferrara N. Role of vascular endothelial growth factor in regu-lation of physiologic alangio genesis.Am J Physiol Cell Physiol, 2001,280: C1358-C1366.
63. Finnin MS, Donigian JR, Cohen A, Richon VM, Rifkind RA, Marks PA, Breslow R, Pavletich NP Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature, 1999, 401:188-193
64. Freeman WM, Walker S J, Vrana KE Quantitative RT-PCR: pitfalls and potential. Biotechniques, 1999, 26:112-22, 124-5
65. Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol, 1987, 196: 261-282
66. Giatromanolaki A. Sivridis E, Athanassou N, Zois E, Thorpe PE, Brekken RA, Gatter KC, Harris AL, Koukourakis IM, Koukourakis MI. Theangio-genic pathway "vascular endothelia lgrowth factor/flk-1(KDR)-reeeptor"in the umatoidarthritis and osteoartltritis. J Pathol, 2001, 194: 101-108
67. Gibson UE, Heid CA, Williams PM. A novel method for real time quantitative RT-PCR. Genome Res, 1996, 6:995-1001
68. Giulietti A, Overbergh L, Valckx D, Decallonne B, Bouillon R, Mathieu C. An overview of real-time quantitative PCR: applications to quantify cytokine gene expression. Methods, 2001,25: 386-401
69. Gockerman A. Prevette T, Jones JI, Clemmons DR. Insulin-like growth factor (IGF)-binding proteins inhibit the smooth muscle cell migration responses to IGF-Ⅰ and IGF-Ⅱ.Endocrinology, 1995. 136:4168-4173
70. Gospodaroeicz D. Localization of a fibrobroblast growth factor and itself fectalone and with hydrocortisonc on 3T3 cell growth.Nature, 1974, 249:123-129
71. Gurbuxani S, Schmitt E, Cande C, Parcellier A, Hammalm A, Daugas E, Kouranti I, Spahr C, Pance A, Kroemer G, Garrido C. Heat shock protein 70 binding inhibits the nuclear import of apoptosis-inducing factor. Oncogene, 2003, 22: 6669-6678.
72. Gustafsson T. Andersson R Arnqvist HJ Different inhibitory actions of IGFBP-1, -2 and -4 on IGF-Ⅰ effects in vascular smooth muscle cells. J J Endocrinol, 1999, 161: 245-53.
73. Hackett JA, Feldser DM, Greider CW. Telomere dysfunction increases mutation rate and genomic instability. Cell, 2001, 106:275-286
74. Hammer C J, Tyler HD, Loskutoff NM, Armstrong DL, Funk DJ, Lindsey BR, Simmons LG Compromised development of calves(Bos gaurus) derived from in vitro-generated embryos and transferred interspecifically into domestic cattle (Bos taurus). Theriogenology, 2001, 55: 1447-55.
75. Han RN, Post M, Tanswell AK, Lye SJ. Insulin-like growth factor-Ⅰ receptor-mediated vasculogenesis/angiogenesis in human lung development. Am J Respir Cell Moi Biol. 2003, 28: 159-69.
76. Harding R, Hooper SB. Regulation of lung expansion and lung growth before birth. J Appl Physiol, 1996, 81:209-24
77. Harley CB, Futcher AB, Greider CW. Telomeres shorten during aging of human fibroblast. Nature, 1990, 345:458-460
78. Hashizume K,Ishiwata H,Kizaki K, Yamada O, Takahashi T, Imai K, Patel OV, Akagi S,Shimizu M,Takahashi S,Katsuma S, Shiojima S, Hirasawa A, Tsyjimoto G, Todoroki J,Izaike Y. Implantation and placental development in somatic cell clone recipient cows. Cloning and Stem Cells, 2002, 4:197-209
79. Heid CA, Stevens J, Livak KJ, Williams PM. Real time quantitative PCR.GenomeRes, 1996, 6: 986-994.
80. Higgis JA, etal. 5' nuclease PCR assay to detect Yersinia pesits. J Clin Microbiol, 1998, 36: 2284-2288.
81. Higuchi R, Dollinger G, Walsh PS, Griffith R. Simultaneous amplification and detection of specific DNA sequences. Biotechnology, 1992,10:413-417.
82. Higuchi R, Fockler C, Dollinger G, Watson R. Kinetic PCR analysis: real-time monitoring of DNA amplification reactions. BioTechnology, 1993, 11:1026-1030
83. Hill JR, Roussel AJ, Cibelli JB, Edwards JF, Hooper NL, Miller MW, Thompson JA, Looney CR, Westhusin ME, Robl JM, Stice SL. Clinical and pathologic features of cloned transgenic calves and fetuses (13 case studies). Theriogenology, 1999, 51:1451-1465
84. Hoch RV, Soriano P. Roles of PDGF in animal development. Development 2003; 130:4769-4784
85. Hogan, BL. Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev, 1996, 10: 1580-1594.
86. Holland PM, Abramson RD, Watson R, Gelfand DH. Detection of specific polymerase chain reaction product by utilizing the 5'----3' exonuclease activity of Thermus aquaticus DNA polymerase. Proc Natl Acad Sci U S A, 1991, 88:7276-7280
87. Holt SE, Shay JW, Wright WE. Refining the telomere-telomerase hypothesis of aging and cancer. Nat Biotechnol, 1996, 14:836-839
88. Howell CY, Bestor TH, Ding F, Latham KE, Mertineit C, Trasler JM, Chaillet JR. Genomic imprinting disrupted by a maternal effect mutation in the Dnmtl gene. Cell, 2001, 104:829-838
89. Humpherys D, Eggan K, Akutsu H, Hochedlinger K, William M. Rideout Ⅲ WM, Biniszkiewicz D, Yanagimachi R, Jaenisch R. Epigenetic Instability in ES Cells and Cloned Mice. Science, 2001,
293: 95-97
90. Humpherys D, Eggan K, Akutsu H, Friedman A, Hochedlinger K. Yauagimachi R. Lander ES, Golub TR, Jaenisch R. Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei. Proc Natl Acad Sci USA, 2002, 99:12889-12894
91. Hunting FW. Brian DH. Breaking the silence in Rett syndrome. Nat Genet,1999, 23:127-128
92. Jaenisch R. DNA methylation and imprinting: why bother? Trends Genet, 1997, 13:323-329
93. Jiao K. Kulessa H. Tompkius K. Zhou Y. Battts L, Baldwin HS. Hogau BL. An essential role of BMP4 in the atrioventricular septation of the mouse heart. Genes Dev, 2003, 17: 2362-2367.
94. Jones JI,Clemmons DR. Insulin-like growth factors and their binding proteins: biological actious. Endicr Rev, 1995, 16:3-34
95. Jones PA DNA methylation errors and cancer. Cancer Res 1996:56:2463-2467
96 Jones PA. Takai D. The Role of DNA Methylation in Mammalian Epigenetics. Science, 2001, 293: 1068
97. Jung J. Zheng M, Goldfarb M; Zaret KS. Initiation of Mammalian Liver Development from Endoderm by Fibroblast Growth Factors.Science, 1999, 284:1998-2003
98. Kalscheuer VM, Mariman EC, Schepens MT, Rehder H, Ropers HH. The insulin-like growth factor type-2 receptor gene is imprinted in the mouse but not in humans. Nat Genet, 1993, 5: 74-8.
99. Kang YK, Koo DB, Park J S, Choi YH, Chung AS, Lee KK, Hart YM. Aberrant methylation of donor genome in cloned bovine embryos. Nat Genet, 2001, 28:173-177
100. Kang YK, Koo DB, Park JS, Choi YH, Kim HN, Chang WK, Lee KK, Han YM. Typical demethylation events in cloned pig embryos. Clues on species-specific differences in epigenetic reprogramming of a cloned donor genome. J Biol Chem, 2001, 276:39980-39984
101. Kang YK. Yeo S, Kim SH, Koo DB, Park JS, Wee G, Han JS, Oh KB, Lee KK, Hart YM. Precise recapitulation of methylation change in early cloned embryos. Mol Reprod Dev, 2003, 66:32-37
102. Kanka J, Hozak E Heyman Y, Chesne E Degrolard J, Renard JE Flechon JE. Transcriptional activity and nucleolar ultrastructure of embryonic rabbit nuclei after transplantation to enucleated oocytes. Mol Reprod Dev, 1996, 43:135-144
103. Kasinathan E Knott JG. Moreira PN, Burnside AS, Jerry D J, Robl JM. Effect of fibroblast donor cell age and cell cycle on development of bovine nuclear transfer embryos in vitro Biol Reprod, 2001, 64:1487-1493
104. Kato Y, Tani T, Sotomaru Y, Kurokawa K, Kato J, Doguchi H, Yasue H, Tsunoda Y. Eight calves cloned from somatic cells of a single adult. Science, 1998, 282:2095-2098
105. Kato Y, Tani T, Tsunoda Y. Cloning of calves from various somatic cell types of male and female adult, newborn and fetal cows. J Reprod Fertil, 2000, 120:231-237
106. Kim KS, Lee YI. Biallelic expression of the H19 and IGF2 genes in hepatocellular carcinoma. Cancer Lett, 1997. 119:143-8
107. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL. Shay JW. Specific association of human telomerase activity with immortal cells and cancer [see comments]. Science, 1994, 266:2011-2015
108. Kishi M, Itagaki Y, Takakura R, Imamura M, Sudo T, Yoshinari M, Tanimoto M, Yasue H, Kashima N Nuclear transfer in cattle using colostrum-derived mammary gland epithelial cells and ear-derived fibroblast cells. Theriogenology, 2000, 54: 675-84.
109. Kitiyanant Y, Saikhun J, Pavasuthipaisit K. Somatic cell nuclear transfer in domestic cat oocytes
treated with IGF-Ⅰ for in vitro maturation. Theriogenology, 2003, 59:1775-86
110. Koo DB, Kang YK, Choi YH, Park JS, Kim HN, Kim T, Lee KK, Han YM. Developmental potential and transgene expression of porcine nuclear transfer embryos using somatic cells. Mol Reprod Dev, 2001, 58:15-21
111. Kubota C, Yamakuchi H, Todoroki J, Mizoshita K, Tabara N, Barber M, Yang X. Six cloned calves produced from adult fibroblast cells after long-term culture. Proc Natl Acad Sci U S A, 2000, 97:990-5
112. Kumar VH, Ryan RM. Growth factors in the fetal and neonatal lung. Front Biosci. 2004, 9: 464-80.
113. Lanza RP, Cibelli JB, Blackwell C, Francis MK, Baerloeher GM, Mak J, Schertzer M, Chavez EA, Sawyer N, Lansdorp PM, West MD. Extension of cell life-span and telomere length in animals cloned from senescent somatic cells, Science, 2000, 288:665-669
114. Lanza RP, Cibelli JB, Faber D, Sweeney RW, Henderson B, Nevala W, West MD, Wettstein PJ. Cloned cattle can be healthy and normal. Science, 2001, 294:1893-4
115. Laurendeau I, Bahuau M, Vodovar N, Larramendy C, Olivi M, Bieche I, Vidaud M, Vidaud D. TaqMan PCR-based gene dosage assay for predictive testing in individuals from a cancer family with INK4 locus haploinsufficiency. Clin Chem, 1999, 45:982-6
116. Lau MM, Stewart CE, Liu Z, Bhatt H, Rotwein P, Stewart CL. Loss of the imprinted IGF2/cation-independent mannose 6-phosphate receptor results in fetal overgrowth and perinatal lethality. Genes Dev, 1994, 8: 2953-63.
117. Lavoir MC, Kelk D, Rumph N, Barnes F, Betteridge KJ, King WA. Transcription and translation in bovine nuclear transfer embryos. Biol Reprod, 1997, 57:204-213
118. Li E, Bestor TH, Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell, 1992, 69:915-926
119. Li E, Beard C, Jaenisch R. Role for DNA methylation in genomic imprinting. Nature, 1993, 366: 362-365
120. Li X, Nong Z, Ekstrom C, Larsson E, Nordlinder H, Hofmann WJ, Trautwein C, Odenthal M, Dienes HP, Ekstrom TJ, Schirmacher P. Disrupted IGF2 promoter control by silencing of promoter P1 in human hepatocellular carcinoma. Cancer Res, 1997, 57:2048-54
121. Liu, J-P, Baker J, Perkins AS, Robertson EJ, Efstratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor Ⅰ(Igf-1) and type 1 IGF receptor (Igflr). Cell, 1993, 75: 59-72
122. Lo YM, Lau TK, Zhang J, Leung TN, Chang AM, Hjelm NM, Elmes RS, Bianchi DW. Increased fetal DNA concentrations in the plasma of pregnant women carrying fetuses with trisomy 21. Clin Chem, 1999, 45:1747-51
123. Ludwig T, Eggenschwiler J, Fisher P, D'Ercole AJ, Davenport ML, Efstratiadis A. Mouse mutants lacking the type 2 IGF receptor (IGF2R) are rescued from perinatal lethality in Igf2 and Igf1r null backgrounds. Dev Biol, 1996, 177:517-535
124. Lyon M E X-chromosome inactivation. Curr Biol, 1999, 8-9:R235～237
125. Mann MR, Chung YG, Nolen LD, Verona RI, Keith E. Latham KE, Bartolomei MS. Disruption of imprinted gene methylation and expression in cloned preimplantation stage mouse embryos. Biol Reprod, 2003, 69:902-914
126. Marahrens Y, Panning B, Dausman J, Strauss W, Jaenisch R Xist-defieient mice are defective in dosage compensation but not spermatogenesis. Genes Dev, 1997, 11:156-66
127. Massague J. TGF beta signal transduction. Annu Rev Biochem, 1998,67:753-791.
128. Mehler MF, Mabie PC, Zhang D, Kessler JA. Bone morphogenetic proteins in the nervous system. Trends Neurosci, 1997, 20:309-317
129. Mertineit C, Yoder JA, Taketo T, Laird DW, Trasler JM, Bestor TH. Sex-specific exons control DNA methyltransferase in mammalian germ cells. Development, 1998, 125:889-897
130. Minoo P. King RJ. Epithelial-mesenehymal interactions in lung development. Annu. Rev. Physiol, 1994.56:13-45
131. Moor T. Haig D. Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet, 1991, 7:45～49
132. Morin-Kensicki EM, Faust C, LaMantia C, Magnuson T. Cell and tissue requirements for the gene eed during mouse gastrul ation and organogenesis.Genesis, 2001,31:142-6
133. Nan X, Campoy FJ, Bird A. MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell. 1997, 88:471-481
134. Neuer A, Spandorfe SD, Giraldo P, Jeremas J, Dieterle S, Korneeva I, Liu HC, Rosenwaks Z, Witkin SS. Heat shock protein expression during gametogenesis and embryogenesis. Infect Dis Obstet Gynecol, 1999, 7:10-16
135. Niemann H. Wrenzycki C Alteration of expression of developmentally important genes in preimplantation bovine embryos by in vitro culture conditions: implications for subsequent development. Theriogeuology, 2000, 53:21-34
136. O'Dell SD, Day IN. Insulin-like growth factor Ⅱ (IGF-Ⅱ). Int J Biochem Cell Biol, 1998, 30: 767-71.
137. Ogawa H, Ono Y, Shimozawa N, Sotomaru Y, Katsuzawa Y, Hiura H, Ito M, Kono T. Disruption of imprinting in cloned mouse fetuses from embryonic stem cells. Reproduction, 2003, 126: 549-557
138. Okano M, Bell DW, Haber DA, Li E, DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development.Cell, 1999, 99:247-257
139. Okano M, Xie S, Li E. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nature Gene, 1998, 19:219-220
140. Oka Y, Waterland RA, Killian JK, Nolan CM, Jang HS, Tohara K, Sakaguchi S, Yao T, Iwashita A, Yata Y, Takahara T, Sato S, Suzuki K, Masuda T, Jirtle RL. M6P/IGF2R tumor suppressor gene mutated in hepatoceilular carcinomas in Japan. Hepatology, 2002, 35:1153-63.
141. Onishi A, Iwamoto M, Akita T, Mikawa S, Takeda K, Awata T, Hanada H, Perry AC. Pig cloning by microinjection of fetal fibroblast nuclei. Science, 2000, 289:1188-1190
142. Panchision DM, Pickel JM, Studer L, Lee SH, Turner PA, Hazel TG, McKay RD. Sequential locations of BMP reseptors control neural precursor cell production and fate. Genes Dev, 2001, 15: 2094-2110.
143. Pan GJ, Chang ZY, Scholer HR, Pei D. Stem cell pluripotency and transcription factor Oct4. Cell Res. 2002, 12:321-329
144. Parks SB, Popovich BW, Press RD. Real-time polymerase chain reaction with fluorescent hybridization probes for the detection of prevalent mutations causing common thrombophilic and iron overload phenotypes. Am J Clin Pathol, 2001, 115: 439-47.
145. Park Y, Kuroda MI.Epigenetic aspects of X-chromosome dosage compensation. Science. 2001 293:1083-5.
146. Penny GD, Kay GF, Sheardown SA, Rastan S, Brockdorff N. Requirement for Xist in the X
chromosome inactivation, Nature, 1996, 379:131-137
147. Pesce M, Sch(?)ler HR. Oct-4: Gatekeeper in the beginnings of mammalian development. Stem Cells, 2001, 19:271-278
148. Powlesland RM, Charles AK, Malik KT, Reynolds PA, Pires S, Boavida M, Brown KW. Loss of heterozygosity at 7p in Wilms' tumour development. Br J Cancer, 2000, 82: 323-9.
149. Qiao J, Bush KT, Steer DL, Stuart RO, Sakurai H, Wachsman W, Nigam SK. Multiple fibroblast growth factors support growth of the ureteric bud but have different effects on branching morphogenesis. Mech Dev, 2001, 109: 123-35.
150. Rajah R, Valentinis B, Cohen P. Insulin-like growth factor(IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-betal on programmed cell death through a p~(53)- and IGF-independent mechanism. J Biol Chem,1997, 272:12181-12188
151. Ratnam S, Mertineit C, Ding F, Howell CY, Clarke HJ, Bestor TH, Chaillet JR, Trasler JM. Dynamics of Dnmtl methyltransferase expression and intracellular localization during oogenesis and preimplantation development. Dev Biol, 2002, 245:,304-314
152. Reik W, Dean W, Walter J. Epigenetic reprogramming in mammalian development. Science, 2001, 293:1089-109
153. Ravelich SR, Breier BH, Reddy S, Keelan JA, Wells DN, James Peterson A, Lee RSE Insulin-Like Growth Factor-Ⅰ and Binding Proteins 1, 2, and 3 in Bovine Nuclear Transfer Pregnancies. Biol. Reprod, 2004, 70:430-438
154. Reynolds TS, Stevenson KR, Wathes DC. Pregnancy-specific alterations in the expression of the insulin-like growth factor system during early placental development in the ewe. Endocrinology, 1997, 138:886-897
155. Richmond EJ, Uzri A, Rogol AD. The insulin-like growth factor system in kidney diseases. Nephron, 2001, 89: 5-9.
156. Richon V M, Emiliani S, Verdin E, Webb Y, Breslow R, Rifldnd RA, Marks PA. A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc Natl Acad Sci U S A, 1998, 95:3003-7.
157. Robertson KD, Keyomarsi K, Gonzales FA, Velicescu M. Jones PA. Differential mRNA expression of the human DNA methyltransferase (DNMTS2)-1, 3a and 3b during G_0G_1 to S phase transition in normal and tumor cells. Nucleic Acids Res, 2000, 28:,2108-2113
158. Roelfsema V, Lane MH, Clark RG. Insulin-like growth factor binding protein (IGFBP) displacers: relevance to the treatment of renal disease. Pediatr Nephrol, 2000, 14: 584-8.
159. Santos F, Zakhartchenko V, Stojkovic M, Peters A, Jenuwein T, Wolf E, Reik W, Dean W. Epigenetie marking correlates with developmental potential in cloned bovine preimplantation embryos. Curr Biol, 2003, 13:1116-1121
160. Schwienbacher C, Angioni A, Scelfo R, Veronese A, Calin GA, Massazza G, Hatada Ⅰ, Barbanti-Brodano G, Negrini M. Abnormal RNA expression of 11 p15 imprinted genes and kidney developmental genes in Wilms' tumor. Cancer Res, 2000, 60:1521-5.
161. Schultz GA, Harvey MB, Watson AJ, et al. Regulation of early embryonic development by growth factors: Growth factor gene expression in cloned bovine embryos. J Animal Sci, 1996, 75: 50-57
162. Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, Yagishita N, Matsui D, Koga Y, Itoh N, Kato S. Fgf10 is essential for limb and lung formation. Nat Genet, 1999, 21: 138-141.
163. Shiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M, Winokur ST, Wasmuth JJ. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia Cell, 1994.78: 335-42.
164. Shibuya M. Structure and function of VEGF/VEGF-receptor system involved in angiogenesis. Cell Struct Funct, 2001,26: 25-
165. Shiels PG. Kind A J, Campbell KH, Waddington D, Wilmut I, Colman A, Schnieke AE. Analysis of telomere lengths in cloned sheep. Nature, 1999, 399:316-317
166. Shimasaki S. Ling N. Identification and molecular characterization of insulin-like growth factor binding proteins(IGFBP-1, -2, -3, -4, -5 and -6). Prog. Growth Factor Res. 3: 243-266, 1991
167. Shin T, K.raemer D, Pryor J, Liu L, Rugila J, Howe L, Buck S, Murphy K, Lyons L, Westhusin M. A cat cloned by nuclear transplantation. Nature, 2002, 415:859
168. Shi W. Zhao J, Anderson KD, Warburton D. Gremlin negatively modulates BMP-4 induction of embryonic mouse lung branching morphogenesis. Am J Physiol Lung Cell Mol Physiol, 2001, 280: L1030-1039.
169. Shi W, Hoeflich A, Flaswinkel H, Stojkovic M, Wolf E, Zakhartchenko V. Induction of a senescent-like phenotype does not confer the ability of bovine immortal cells to support the development of nuclear transfer embryos. Biol Reprod, 2003, 69:301-309
170. Smith SD, Soloy E, Kanka J, Holm P, Callesen H. Influence of recipient cytoplasm cell stage on transcription in bovine nucleus transfer embryos. Mol Reprod Dev, 1996, 45:444-450
171. Steiling H, Wustefeld T, Bugnon P, Brauchle M, Fassler R. Teupser D, Thiery. J, Gordon JI, Trautweiu C, Werner S. Fibroblast growth factor receptor signalling is crucial for liver homeostasis and regeneration. Oncogene, 2003, 22:4380-8
172. Stice SL, Robl JM, Ponce de Leon FA, Jerry J, Golueke PJ, Cibelli JB, Kane JJ. Cloning: new breakthroughs leading to commercial opportunities. Theriogenology, 1998, 49:129-138
173. Sun CE Lee CH, Cheng SW, Lin MH, Wu TL, Tsao KC, Chiu DT, Liou JD, Chu DC. Real-time quantitative PCR analysis for alpha-thalassemia-1 of Southeast Asian type deletion in Taiwan. Clin Genet, 2001, 60:305-9
174. Sun FL, Dean WL, Kelsey G, Allen, ND, Raik, W. Transactivation of Igf2 in a mouse model of Beckwith-Wiedemann syndrome. Nature, 1997, 389:809-815
175. Ten Have-Opbroek AA. Lung development in the mouse embryo. Exp Lung Res, 1991, 17: 111-30.
176. Tian XC, Xu J, Yang X. Normal telomere lengths found in cloned cattle. Nature Genet, 2000, 26: 272～273
177. Tsujiuchi T, Sasaki Y, Oka Y, Kuniyasu H, Konishi Y, Tsutsumi M. Alterations of the M6p/tgf2 receptor gene in hepatocellular carcinomas induced by N-nitrosodiethylamine and a choline-deficient L-amino acid-defined diet in rats. Mol Carcinog, 2004, 39:199-205
178. Tyagi S, Kramer FR. Molecular beacons: probes that fluoresce upon hybridization Nat-Biotechol, 1996, 14:303-308
179. Urist MR. Bone formation by auto induction. Science, 1965, 150:893-899
180. Vanden Veyver IB, Zoghbi HY. Methyl-CpG-binding protein 2 mutations in Rett syndrome. Curt Opin Genet Devel, 2000, 10275-279
181. Van der Vtag J, Otte AP. Transcriptional repression mediated by the human polycomb-group protein E ED involves histone deacetylation. Nat Genet, 1999, 23: 474-8
182. Van Stekelenburg-Hamers AE, Rebel HG, Van Inzen WG, de Loos FA, Drost M, Mummery CL,
Weima SM, Trounson AO. Stage-specific appearance of the mouse antigenTEC-3 innormal and nuclear transfer bovine embryos: Re-expression after nuclear transfer. Mol Reprod Dev, 1995, 37: 27～33
183. Vertino PM, Yen R-WC, Gao J, Baylin SB. De novo methylation of CpG island sequences in human fibroblasts overexpressing DNA(cysteine 5)-methyltransferase. Mol Cell Biol, 1996, 16: 4555-4565
184. Wakayama T, Perry ACF, Zuccotti M, Johnson KR, Yanagimachi R. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature, 1998, 394:369-373
185. Wakayama T, Tateno H, Mombaerts P, Yanagimachi R. Nuclear transfer into mouse zygotes. Nat Genet, 20(10, 24:108-109
186. Walburger DK, Afonina IA, Wydro R. An improved real time PCR method for simultaneous detection of C282Y and H63D mutations in the HFE gene associated with hereditary hemochromatosis. Mutat Res, 2001, 432:69-78
187. Walker NJ. Real-time and quantitative PCR: applications to mechanism-based toxicology. J Biochem Mol Toxicol, 2001, 15:121-7
188. Wall RJ, Kerr DE, Bondioli KR. Transgenic dairy cattle: genetic engineering on a large scale. J Dairy Sci, 1997, 80:2213-2224
189. Wang J, Mager J, Chert Y, Schneider E, Cross JC, Nagy A, Magnuson T.Imprinted X inactivation maintained by a mouse Polycemb group gene. Nat Genet, 2001, 28:371-5
190. Wang J, Mager J, Schnedier E, Magnuson T. The mouse PeG gene cod is required for Hox gene repression and extraembryonic development.Mature Genome, 2002, 13:493-503
191. Wang X, Li X, Willette RN, Barone FC, Feuerstein GZ. Application of real-time polymerase chain reaction to quantitate induced expression of interleukin-1 beta mRNA in ischemic brain tolerance. Neurosci Res, 2000, 59:238-46
192. MeKeehan WL, Wang F, Kan M. The heparan sulfate-fibroblast growth factor family: diversity of structure and function. Prog Nucleic Acids Res Mol Biol, 1998, 59:135-176
193. Weaver M, Dunn NR, Hogan BL. BMP4 and Fgf10 play opposing roles during lung bud morphogenesis. Development, 2000, 127:2695-2704
194. Wells DN, Misica PM, Tervit HR. Production of cloned calves following nuclear transfer with cultured adult mural granulosa cells. Biol Reprod, 1999, 60:996-1005
195. Wetteran LA, Moore MG, Lee KW, Shim ML, Cohen P. Novel aspects of the insulin-like growth factor binding proteins. Mol Genet Metab, 1999, 68:161-181
196. Wells DN, Misica PM, Tervit HR, Vivanco WH. Adult somatic cell nuclear transfer is used to preserve the last surviving cow of the Enderby Island cattle breed. Reprod Fertil Dev, 1998, 10: 369-78.
197. Wilmut I, Schnieke AE, McWhir J, Kind KL, Campbell KHS. Viable offspring derived from fetal and adult mammalian cells, Nature, 1997, 385:810-813.
198. Wilmut I. Cloning for medicine. Sci Am, 1998, 279:58-63
199. Wilmut I, Beaujean N, Somatic cell nuclear transfer. Nature, 2002, 419:583-585
200. Winger QA, Hill JR, Shin T, Watson AJ, Kraemer DC, Westhusin ME. Genetic reprogramming of lactate dehydrogenase, citrate synthase, and phosphofructokinase mRNA in bovine nuclear transfer embryos produced using bovine fibroblast cell nuclei. Mol Reprod Dev; 2000, 56: 458-464
201. Wittwer CT, Herrmann MG, Moss AA, Rasmussen RP. Continuous fluorescence monitoring of
rapid cycle DNA amplification. Biotechniques, 1997, 22:130-1,134-8
202. Wittwer CT. Ririe KM, Andrew RV. David DA, Gundry RA, Balis UJ. The LightCycler: a microvolume multisample fluorimeter with rapid temperature control. Biotechniques, 1997, 22:176-181
203. Wu J, Issa J-P, Herman J, Bassett DE, Nellkin BD, Baylin SB Expression of an exogenous eukaryotic DNA methyltransferase gene induces transformation of NIH 3T3 cells. Proc Natl Acad Sci U S A, 1993; 90:8891-8895
204 Wrenzycki C, Wells D, Herrmann D, Miller A, Oliver J, Tervit R. Niemann H. Nuclear transfer protocol affects messenger RNA expression patterns in cloned bovine blastocysts. Biol Reprod, 2001,65:309-317
205. Wrenzycki C, Lucas-Halm A, Herrmann D, Lemme E, Korsawe K, Niemann H. In vitro roduction and nuclear transfer affect dosage compensation of the X-linked gene transcripts G6PD, PGK, and Xist in preimplantation bovine embryos. Biol Reprod, 2002; 66: 127-134.
206. Xue E Tian XC, Du F, Taneja M, Dinnyes A, Dai Y, Levine H, Pereira LV, Yang X. Aberrant patterns of X chromosome inactivation in bovine clones. Nat Genet, 2002, 31:216-219.
207. Wu XR, Zao DH, Lin Q, Bu DF, Zuo CH. Rett syndrome in China: report of 9 patients. Pediatr Neurol, 1988, 4:126-127
208. Xu YQ, Grundy P, Polychronakos C. Aberrant imprinting of the insulin-like growth factor Ⅱ receptor gene in Wilms' tumor. Oncogene, 1997,14: 1041-6.
209. Yakar S. The role of circulating IGF-Ⅰ: lessons from human and animal models. Endocnne, 2002, 19:239-248
210. Yamauchi T. Yamauchi J, Kuwata T, Tamura T, Yamashita T, Bae N, Westphal H. Ozato K, Nakatani Y. Distinct but overlapping roles of historic acetylase PCAF and of the closely related PCAF-B/GCN5 in mouse embryogenesis. PNAS, 2000, 97:11303-11306.
211. Young LE, Fernandes K, McEvoy TG, Butterwith SC, Gutierrez CG, Carolan C, Broadbent PJ, Robinson JJ, Wilmut I, Sinclair KD. Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat Genet, 2001, 27:153-154
212. Young LE, Schnieke AE, McCreath K J, Wieckowski S, Konfortova G, Fernandes K, Ptak G, Kind AJ. Wilmut I, Loi P, Feil R. Conservation of IGF2-H19 and IGF2R impnnting in sheep: effects of somatic cell nuclear transfer. Mech Dev, 2003, 120:1433-1442
213. Zhao GQ. Consequences of knocking out BMP signaling in the mouse. Genesis, 2003, 35:43-56
214. Schwienbacher C, Angioni A, Scelfo R, Veronese A, Calin GA, Massazza G. Hatada I, Barbanti-Brodano G, Negrini M Abnormal RNA expression of 11 p15 imprinted genes and kidney developmental genes in Wilms' tumor. Cancer Res, 2000, 60:1521-5
215．秦鹏春，哺乳动物脴胎．北京：科学出版社，2000，397～398
2. Abboud HE. Role of platelet-derived growth factor in renal injury. Annu Rev Physiol, 1995, 57: 297-309
3. Agabiti-Rosei E, Muiesan ML Prognostic significance of left ventricular hypertrophy regression. Adv Exp Med Biol, 1997, 432:199-205
4. Aonymous.Translational research:the role of VEGF intu-morangiogenesis. Proceedings of asymposium. Oncologist, 2000, 5(Supp 11): 1-57
5. Anversa P, Nadal-Ginard B Myocyte renewal and ventricular remodelling Nature, 2002, 415: 240-3
6. Arat S, Rzucidlo SJ, Gibbons J, Miyoshi K, Stice SL. Production of transgenic bovine embryos by transfer of transfected granulosa cells into enucleated oocytes. Mol Reprod Dev, 2001, 60: 20-6
7. Arman E, Haffner-Krausz R, Chen Y, Heath JK, Lonai P. Targeted disruption of fibroblast growth factor(FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development. Proc Natl Acad Sci U S A, I998, 95:5082-7
8. Arman E, Haffner-Krausz R, Gorivodsky M, Lonai P. Fgfr2 is required for limb outgrowth and lung-branching morphogenesis. Proc Natl Aead Sei U S A 1999; 96:11895-11899
9. Baguisi A, Behboodi E, Melican DT, Pollock JS, Destrempes MM, Cammuso C, Williams JL, Nims SD, Porter CA, Midura P, Palaeios MJ, Ayres SL, Denniston RS, Hayes ML, Ziomek CA, Meade HM, Godke RA, Gavin WG, Overstrom EW, Echelard Y. Production of goats by somatic cell nuclear transfer. Nat Biotechnol, 1999, 17:456-461
10. Barlow DP. Genomic imprinting in mammalian. Science, 1995, 270:1610-1613
11. Bauer MK, Harding JE, Bassett NS, Breier BH, Oliver MH, Gallaher BH, Evans PC, Woodall SM, Gluckman PD. Fetal growth and placental function. Mol Cell Endocrinol, 1998, 140:115-120
12. Beeker K, Pan D, Whitely CB. Real-time quantitative polymerase chain reaction to assess gene transfer. Hum Gene Ther, 1999, 10:2559-2566
13. Bellusci S, Henderson R, Winnier G, Oikawa T, Hogan BL. Evidence from normal expression and targeted misexpression that bone morphogenetic protein (Bmp-4) plays a role in mouse embryonic lung morphogenesis. Development, 1996, 122:1693-1702
14. Betts DH, Bordignon V, Hill J K, Winger Q, Westhusin ME, Smith LC, King WA. Reprogramming of telomerase activity and rebuilding of telomere length in cloned cattle. Proc Natl Acad Sci USA, 2001, 98:1077-1082
15. Bieche I, Oondy E Laurendeau I, Olivi M, Vidaud D, Lidereau R, Vidaud M. Real-time reverse transcription-PCR assay for future nagement of ERBB2-based clinical apolications. Clin Chem, 1999, 45:1148-1156
16. Biniszkiewicz D, Gribnau J, Ramsahoye B, Gaudet F, Eggan K, Humpherys D, Mastrangelo M-A, Jun Z, Walter J, Jaenisch R. Dnmtl Overexpression Causes Genomic Hypermethylation, Loss of
Imprinting, and Embryonic Lethality. Molecular and Cellular Biology, 2002, 22:2124-2135
17. Bird AP. Wolffe AP. Methylation-induced repression—belts, braces, and chromatin. Cell. 1999. 99:451-454
18. Bostrom H. Gritli-Linde A, Betsholtz C. PDGF-A/PDGF alpha-receptor signaling is required for lung growth and the formation of alveoli but not for early lung branching morphogenesis. Dev Dvn. 2002, 223:155-162
19. Bourc'his D. Le Bourhis D, Patin D, Niveleau A, Comizzoli E Renard JR Viegas-Pequignot E. Delaved and incomplete reprogramming of chromosome methylation pattenrns in bovine cloned embryos. Curr Biol. 2001, 11:1542-1546
20. Brockdorff N. The role of Xist in X-inactivation. Curr Opin Genet Dev, 1998.8:328-333
21. Brown KW. Villar AJ, Bickmore W, Clayton-Smith J, Catchpoole D, Maher ER, Reik W Imprinting mutation in the Beckwith-Wiedemann syndrome leads to biallelic IGF2 expression through an H19-independent pathway. Hum Mol Genet, 1996, 5:2027-2032
22. Campbell KH, McWhir J, Ritchie WA, Wilmut I. Sheep cloned by nuclear transfer from a cultured cell line Nature, 1996, 380:64-66
23. Cancilla B. Ford-Perriss MD, Bertram JE Expression and localization of fibroblast growth factors and fibroblast growth factor receptors in the developing rat kidney. Kidney Int, 1999, 56: 2025-39.
24. Carlson LL, Page AW, Bestor TH. Properties and localization of DNA methyltransferase in preimplantation mouse embryos: implications for genomic imprinting. Genes Dev, 1992, 6: 2536-2541
25. Carmeliet R Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature, 1996, 380:435-439
26. Cezar GG Bartolomei MS, Forsberg E J, First NL, Bishop MD, Eilertsen KJ. Genome-wide epigenetic alterations in cloned bovine fetuses. Biol Reprod, 2003, 68:1009-1014
27. Chao W. Huynh KD, Spencer RJ, Davidow LS, Lee JT. CTCF, a candidate trans-acting factor for X-inactivation choice. Science, 2002, 295:345-7
28. Chavatte-Palmer P, Heyman Y, Richard C, Monger P, LeBourhis D, Kann G, Chilliard Y, Vignon X, Renard JP. Clinical, hormonal, and hematologic characteristics of bovine calves derived from nuclei from somatic cells. Biol Reprod, 2002, 66:1596-1603
29. Chen Z, Yung WK. A reliabili.ty test of standard-based quantitative PCR: exogenous vs endogenous standards. Mol. Cell Probes. 2000, 14:127-135
30. Chesne P, Adenot PG, Viglietta C, Baratte M, Boulanger L, Renard JP. Cloned rabbits produced by nuclear transfer from adult somatic cells. Nat Biotechnol, 2002, 20:366-369
31. Cibelli JB. Stice SL, Golueke P J, Kane JJ, Jerry J, Blackwell C, Ponce de Leon FA, Robl JM. Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science, 1998, 280: 1256-8
32. Chien KR, Zhu H, Knowlton KU, Miller-Hance W, van-Bilsen M, O'Brien TX, Evans SM. Transcriptional regulation during cardiac growth and development. Annu Rev Physiol, 1993, 55: 77-95
33. Chung YG. Ratnam S, Chaillet JR, Latham KE. Abnormal regulation of DNA methyltransferase expression in cloned mouse embryos. Biol Reprod, 2003, 69:146-153
34. Connolcy DT Vascular permeability factor:aunique regulator of blood vessel function. J Cell Biochem, 1991,47: 219-223
35. Costes B, Girodon E, Vidaud D, Flori E, Ardalan A, Conteville P, Fanen P, Niel F, Vidaud M, Goossens M. Prenatal detection by real-time quantitative PCR and characterization of a new CFTR deletion, 3600+15kbde15.3kb (or CFTRdele19). Clin Chem, 2000, 46:1417-20
36. Counter CM, Avilion AA, LeFeuvre CE, Stewart NG, Greider CW, Harley CB, Bacchetti S. Telomere shortening associated with chromosome instability is arrested in immortal ceils which express telomerase activity. EMBO J, 1992, 11 : 1921-1929
37. Cuevas P, Burgos J, Baird A. Basic fibrobroblast growth factor(FGF) promote scartilege repair in vivo. Biochem Biophys Res Commun, 1988, 156:611-618
38. Daniel TO, Kumjian DA. Platelet-derived growth factor in renal development and disease. Semin Nephrol, 1993, 13:87-95
39. Daniels R, Hall V, Trounson AO. Analysis of gene transcription in bovine nuclear transfer embryos reconstructed with granulosa cell nuclei. Biol Reprod, 2000, 63:1034-1040
40. Daniels R, Hall VJ, French AJ, Korfiatis NA, and Trounson AO. Comparison of gene transcription in cloned bovine embryos produced by different nuclear transfer techniques. Mol Reprod Dev, 2001, 60:281-288
41. Davie JR. Covalent modifications of histones: expression from chromatin templates. Curr Opin Genet Dev, 1998, 8:173-8
42. Davis TL, Yang GJ, McCarrey JR, Bartolomei MS. The H19 methylation impnnt is erased and re-established differentially on the parental alleles during male germ cell development. Hum Mol Genet, 2000, 9:2885-2894
43. Dean W, Santos F, Stojkovic M, Zakhartchenko V, Walter J, Wolf E, Reik W. Conservation of methylation reprogramming in mammalian development: aberrant reprogramming in cloned embryos. Proc Natl Acad Sci U S A, 2001, 98:13734-13738
44. DeChiara TM, Efstratiadis A, and Robertson EJ. A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor Ⅱ gene disrupted by targeting. Nature, 1990, 345: 78-80
45. Delot EC, Bahamonde ME, Zhao M, Lyons KM. BMP signaling is required for septation of the outflow tract of the mammalian heart. Development, 2003, 130: 209-220.
46. Delot EC. Control of endocardial cushion and cardiac valve maturation by BMP signaling pathways. Mol Genet Metab, 2003, 80: 27-35.
47. Deng CX, Wynshaw-Boris A, Shen MM, Daugherty C, Ornitz DM, Leder P. Murine FGFR-1 is required for early postimplantation growth and axial organization. Genes Dev, 1994, 8: 3045-3057.
48. DiFiore JW, Wilson JM. Lung development. Seminars in Pediatric Surgery., 1994, 3:221-32
49. Dor Y, Klewer SE, McDonald JA, Keshet E, Camenisch TD. VEGF modulates early heart valve formation. Anat Rec, 2003, 271A: 202-208
50. Dupont J, Holzenberger M. Biology of insulin-like growth factors in development. Birth Defects Res Part C Embryo Today, 2003, 69:257-71
51. Du Z, Cong H, Yao Z. Identification of putative downstream genes of Oct-4 by suppression-subtractive hybridization. Biochem Biophys Res Commun, 2001,282:701-706
52. Ebendal T, Bengtsson H, Soderstrom S. Bone morphogenetic proteins and their receptors: potential functions in the brain. Neurosci Res, 1998, 51:139-146
53. Egawa C. Mivoshi Y. Takamura Y, Taguchi T, Tamaki Y, Noguchi S. Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancer, Int J Cancer, 2001, 95: 255-9
54. Eggan K. Akutsu H. Hochedlinger K, Rideout W. Yanagimachi R. Jaenisch R..X-Ctu-omosome inactivation in cloned mouse embryos. Science, 2000, 290:1578-1581
55. Enright BP, Jeong BS, Yang X, Tian XC. Epigenetic characteristics of bovine donor cells for nuclear transfer: levels of histone acetylation. Biol Reprod, 2003, 69: 1525-1530
56. Enright BP, Kubota C, Yang X, Tian XC. Epigenetic characteristics and development of embryos cloned from donor cells treated by trichostatin A or 5-aza-2'-deoxytytidine. Biol Reprod, 2003, 69 896-901
57. Ezashi T. Ghosh D, Roberts R M. Repression of Ets-2-induced transactivaton of the tau interferon promoter by Oct-4. Mol Cell Biol, 2001, 21:7883-7891
58. Faragher RG. Kipling D. How might replicative senescence contribute to human aging? Bioessays, 1998, 20:985-991
59. Fei X, Tian XC, Du FL, Kubota C, Taneja-M, Dirnnyes A, Dai YR Levine H, Yang X. Aberrant patterns of X chromosome inactiviation in bovine clones. Nat Geuet, 2002, 31: 216-219.
60. Ferrara N, Henzel WJ .Pituitary follicular cells secrete anove heparin-binding growth factor specific for vascular endothelia cells. Biochem Biophys Res Commun, 1989, 161: 851858.
61. Ferrara N, Carvermoore K, Chen H, Dowd M, Lu L, Oshea KS, Powellbraxton L, Hillan KJ, Moore MW Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature, 1996, 380: 439-442.
62. Ferrara N. Role of vascular endothelial growth factor in regu-lation of physiologic alangio genesis.Am J Physiol Cell Physiol, 2001,280: C1358-C1366.
63. Finnin MS, Donigian JR, Cohen A, Richon VM, Rifkind RA, Marks PA, Breslow R, Pavletich NP Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature, 1999, 401:188-193
64. Freeman WM, Walker S J, Vrana KE Quantitative RT-PCR: pitfalls and potential. Biotechniques, 1999, 26:112-22, 124-5
65. Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol, 1987, 196: 261-282
66. Giatromanolaki A. Sivridis E, Athanassou N, Zois E, Thorpe PE, Brekken RA, Gatter KC, Harris AL, Koukourakis IM, Koukourakis MI. Theangio-genic pathway "vascular endothelia lgrowth factor/flk-1(KDR)-reeeptor"in the umatoidarthritis and osteoartltritis. J Pathol, 2001, 194: 101-108
67. Gibson UE, Heid CA, Williams PM. A novel method for real time quantitative RT-PCR. Genome Res, 1996, 6:995-1001
68. Giulietti A, Overbergh L, Valckx D, Decallonne B, Bouillon R, Mathieu C. An overview of real-time quantitative PCR: applications to quantify cytokine gene expression. Methods, 2001,25: 386-401
69. Gockerman A. Prevette T, Jones JI, Clemmons DR. Insulin-like growth factor (IGF)-binding proteins inhibit the smooth muscle cell migration responses to IGF-Ⅰ and IGF-Ⅱ.Endocrinology, 1995. 136:4168-4173
70. Gospodaroeicz D. Localization of a fibrobroblast growth factor and itself fectalone and with hydrocortisonc on 3T3 cell growth.Nature, 1974, 249:123-129
71. Gurbuxani S, Schmitt E, Cande C, Parcellier A, Hammalm A, Daugas E, Kouranti I, Spahr C, Pance A, Kroemer G, Garrido C. Heat shock protein 70 binding inhibits the nuclear import of apoptosis-inducing factor. Oncogene, 2003, 22: 6669-6678.
72. Gustafsson T. Andersson R Arnqvist HJ Different inhibitory actions of IGFBP-1, -2 and -4 on IGF-Ⅰ effects in vascular smooth muscle cells. J J Endocrinol, 1999, 161: 245-53.
73. Hackett JA, Feldser DM, Greider CW. Telomere dysfunction increases mutation rate and genomic instability. Cell, 2001, 106:275-286
74. Hammer C J, Tyler HD, Loskutoff NM, Armstrong DL, Funk DJ, Lindsey BR, Simmons LG Compromised development of calves(Bos gaurus) derived from in vitro-generated embryos and transferred interspecifically into domestic cattle (Bos taurus). Theriogenology, 2001, 55: 1447-55.
75. Han RN, Post M, Tanswell AK, Lye SJ. Insulin-like growth factor-Ⅰ receptor-mediated vasculogenesis/angiogenesis in human lung development. Am J Respir Cell Moi Biol. 2003, 28: 159-69.
76. Harding R, Hooper SB. Regulation of lung expansion and lung growth before birth. J Appl Physiol, 1996, 81:209-24
77. Harley CB, Futcher AB, Greider CW. Telomeres shorten during aging of human fibroblast. Nature, 1990, 345:458-460
78. Hashizume K,Ishiwata H,Kizaki K, Yamada O, Takahashi T, Imai K, Patel OV, Akagi S,Shimizu M,Takahashi S,Katsuma S, Shiojima S, Hirasawa A, Tsyjimoto G, Todoroki J,Izaike Y. Implantation and placental development in somatic cell clone recipient cows. Cloning and Stem Cells, 2002, 4:197-209
79. Heid CA, Stevens J, Livak KJ, Williams PM. Real time quantitative PCR.GenomeRes, 1996, 6: 986-994.
80. Higgis JA, etal. 5' nuclease PCR assay to detect Yersinia pesits. J Clin Microbiol, 1998, 36: 2284-2288.
81. Higuchi R, Dollinger G, Walsh PS, Griffith R. Simultaneous amplification and detection of specific DNA sequences. Biotechnology, 1992,10:413-417.
82. Higuchi R, Fockler C, Dollinger G, Watson R. Kinetic PCR analysis: real-time monitoring of DNA amplification reactions. BioTechnology, 1993, 11:1026-1030
83. Hill JR, Roussel AJ, Cibelli JB, Edwards JF, Hooper NL, Miller MW, Thompson JA, Looney CR, Westhusin ME, Robl JM, Stice SL. Clinical and pathologic features of cloned transgenic calves and fetuses (13 case studies). Theriogenology, 1999, 51:1451-1465
84. Hoch RV, Soriano P. Roles of PDGF in animal development. Development 2003; 130:4769-4784
85. Hogan, BL. Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev, 1996, 10: 1580-1594.
86. Holland PM, Abramson RD, Watson R, Gelfand DH. Detection of specific polymerase chain reaction product by utilizing the 5'----3' exonuclease activity of Thermus aquaticus DNA polymerase. Proc Natl Acad Sci U S A, 1991, 88:7276-7280
87. Holt SE, Shay JW, Wright WE. Refining the telomere-telomerase hypothesis of aging and cancer. Nat Biotechnol, 1996, 14:836-839
88. Howell CY, Bestor TH, Ding F, Latham KE, Mertineit C, Trasler JM, Chaillet JR. Genomic imprinting disrupted by a maternal effect mutation in the Dnmtl gene. Cell, 2001, 104:829-838
89. Humpherys D, Eggan K, Akutsu H, Hochedlinger K, William M. Rideout Ⅲ WM, Biniszkiewicz D, Yanagimachi R, Jaenisch R. Epigenetic Instability in ES Cells and Cloned Mice. Science, 2001,
293: 95-97
90. Humpherys D, Eggan K, Akutsu H, Friedman A, Hochedlinger K. Yauagimachi R. Lander ES, Golub TR, Jaenisch R. Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei. Proc Natl Acad Sci USA, 2002, 99:12889-12894
91. Hunting FW. Brian DH. Breaking the silence in Rett syndrome. Nat Genet,1999, 23:127-128
92. Jaenisch R. DNA methylation and imprinting: why bother? Trends Genet, 1997, 13:323-329
93. Jiao K. Kulessa H. Tompkius K. Zhou Y. Battts L, Baldwin HS. Hogau BL. An essential role of BMP4 in the atrioventricular septation of the mouse heart. Genes Dev, 2003, 17: 2362-2367.
94. Jones JI,Clemmons DR. Insulin-like growth factors and their binding proteins: biological actious. Endicr Rev, 1995, 16:3-34
95. Jones PA DNA methylation errors and cancer. Cancer Res 1996:56:2463-2467
96 Jones PA. Takai D. The Role of DNA Methylation in Mammalian Epigenetics. Science, 2001, 293: 1068
97. Jung J. Zheng M, Goldfarb M; Zaret KS. Initiation of Mammalian Liver Development from Endoderm by Fibroblast Growth Factors.Science, 1999, 284:1998-2003
98. Kalscheuer VM, Mariman EC, Schepens MT, Rehder H, Ropers HH. The insulin-like growth factor type-2 receptor gene is imprinted in the mouse but not in humans. Nat Genet, 1993, 5: 74-8.
99. Kang YK, Koo DB, Park J S, Choi YH, Chung AS, Lee KK, Hart YM. Aberrant methylation of donor genome in cloned bovine embryos. Nat Genet, 2001, 28:173-177
100. Kang YK, Koo DB, Park JS, Choi YH, Kim HN, Chang WK, Lee KK, Han YM. Typical demethylation events in cloned pig embryos. Clues on species-specific differences in epigenetic reprogramming of a cloned donor genome. J Biol Chem, 2001, 276:39980-39984
101. Kang YK. Yeo S, Kim SH, Koo DB, Park JS, Wee G, Han JS, Oh KB, Lee KK, Hart YM. Precise recapitulation of methylation change in early cloned embryos. Mol Reprod Dev, 2003, 66:32-37
102. Kanka J, Hozak E Heyman Y, Chesne E Degrolard J, Renard JE Flechon JE. Transcriptional activity and nucleolar ultrastructure of embryonic rabbit nuclei after transplantation to enucleated oocytes. Mol Reprod Dev, 1996, 43:135-144
103. Kasinathan E Knott JG. Moreira PN, Burnside AS, Jerry D J, Robl JM. Effect of fibroblast donor cell age and cell cycle on development of bovine nuclear transfer embryos in vitro Biol Reprod, 2001, 64:1487-1493
104. Kato Y, Tani T, Sotomaru Y, Kurokawa K, Kato J, Doguchi H, Yasue H, Tsunoda Y. Eight calves cloned from somatic cells of a single adult. Science, 1998, 282:2095-2098
105. Kato Y, Tani T, Tsunoda Y. Cloning of calves from various somatic cell types of male and female adult, newborn and fetal cows. J Reprod Fertil, 2000, 120:231-237
106. Kim KS, Lee YI. Biallelic expression of the H19 and IGF2 genes in hepatocellular carcinoma. Cancer Lett, 1997. 119:143-8
107. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL. Shay JW. Specific association of human telomerase activity with immortal cells and cancer [see comments]. Science, 1994, 266:2011-2015
108. Kishi M, Itagaki Y, Takakura R, Imamura M, Sudo T, Yoshinari M, Tanimoto M, Yasue H, Kashima N Nuclear transfer in cattle using colostrum-derived mammary gland epithelial cells and ear-derived fibroblast cells. Theriogenology, 2000, 54: 675-84.
109. Kitiyanant Y, Saikhun J, Pavasuthipaisit K. Somatic cell nuclear transfer in domestic cat oocytes
treated with IGF-Ⅰ for in vitro maturation. Theriogenology, 2003, 59:1775-86
110. Koo DB, Kang YK, Choi YH, Park JS, Kim HN, Kim T, Lee KK, Han YM. Developmental potential and transgene expression of porcine nuclear transfer embryos using somatic cells. Mol Reprod Dev, 2001, 58:15-21
111. Kubota C, Yamakuchi H, Todoroki J, Mizoshita K, Tabara N, Barber M, Yang X. Six cloned calves produced from adult fibroblast cells after long-term culture. Proc Natl Acad Sci U S A, 2000, 97:990-5
112. Kumar VH, Ryan RM. Growth factors in the fetal and neonatal lung. Front Biosci. 2004, 9: 464-80.
113. Lanza RP, Cibelli JB, Blackwell C, Francis MK, Baerloeher GM, Mak J, Schertzer M, Chavez EA, Sawyer N, Lansdorp PM, West MD. Extension of cell life-span and telomere length in animals cloned from senescent somatic cells, Science, 2000, 288:665-669
114. Lanza RP, Cibelli JB, Faber D, Sweeney RW, Henderson B, Nevala W, West MD, Wettstein PJ. Cloned cattle can be healthy and normal. Science, 2001, 294:1893-4
115. Laurendeau I, Bahuau M, Vodovar N, Larramendy C, Olivi M, Bieche I, Vidaud M, Vidaud D. TaqMan PCR-based gene dosage assay for predictive testing in individuals from a cancer family with INK4 locus haploinsufficiency. Clin Chem, 1999, 45:982-6
116. Lau MM, Stewart CE, Liu Z, Bhatt H, Rotwein P, Stewart CL. Loss of the imprinted IGF2/cation-independent mannose 6-phosphate receptor results in fetal overgrowth and perinatal lethality. Genes Dev, 1994, 8: 2953-63.
117. Lavoir MC, Kelk D, Rumph N, Barnes F, Betteridge KJ, King WA. Transcription and translation in bovine nuclear transfer embryos. Biol Reprod, 1997, 57:204-213
118. Li E, Bestor TH, Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell, 1992, 69:915-926
119. Li E, Beard C, Jaenisch R. Role for DNA methylation in genomic imprinting. Nature, 1993, 366: 362-365
120. Li X, Nong Z, Ekstrom C, Larsson E, Nordlinder H, Hofmann WJ, Trautwein C, Odenthal M, Dienes HP, Ekstrom TJ, Schirmacher P. Disrupted IGF2 promoter control by silencing of promoter P1 in human hepatocellular carcinoma. Cancer Res, 1997, 57:2048-54
121. Liu, J-P, Baker J, Perkins AS, Robertson EJ, Efstratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor Ⅰ(Igf-1) and type 1 IGF receptor (Igflr). Cell, 1993, 75: 59-72
122. Lo YM, Lau TK, Zhang J, Leung TN, Chang AM, Hjelm NM, Elmes RS, Bianchi DW. Increased fetal DNA concentrations in the plasma of pregnant women carrying fetuses with trisomy 21. Clin Chem, 1999, 45:1747-51
123. Ludwig T, Eggenschwiler J, Fisher P, D'Ercole AJ, Davenport ML, Efstratiadis A. Mouse mutants lacking the type 2 IGF receptor (IGF2R) are rescued from perinatal lethality in Igf2 and Igf1r null backgrounds. Dev Biol, 1996, 177:517-535
124. Lyon M E X-chromosome inactivation. Curr Biol, 1999, 8-9:R235～237
125. Mann MR, Chung YG, Nolen LD, Verona RI, Keith E. Latham KE, Bartolomei MS. Disruption of imprinted gene methylation and expression in cloned preimplantation stage mouse embryos. Biol Reprod, 2003, 69:902-914
126. Marahrens Y, Panning B, Dausman J, Strauss W, Jaenisch R Xist-defieient mice are defective in dosage compensation but not spermatogenesis. Genes Dev, 1997, 11:156-66
127. Massague J. TGF beta signal transduction. Annu Rev Biochem, 1998,67:753-791.
128. Mehler MF, Mabie PC, Zhang D, Kessler JA. Bone morphogenetic proteins in the nervous system. Trends Neurosci, 1997, 20:309-317
129. Mertineit C, Yoder JA, Taketo T, Laird DW, Trasler JM, Bestor TH. Sex-specific exons control DNA methyltransferase in mammalian germ cells. Development, 1998, 125:889-897
130. Minoo P. King RJ. Epithelial-mesenehymal interactions in lung development. Annu. Rev. Physiol, 1994.56:13-45
131. Moor T. Haig D. Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet, 1991, 7:45～49
132. Morin-Kensicki EM, Faust C, LaMantia C, Magnuson T. Cell and tissue requirements for the gene eed during mouse gastrul ation and organogenesis.Genesis, 2001,31:142-6
133. Nan X, Campoy FJ, Bird A. MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell. 1997, 88:471-481
134. Neuer A, Spandorfe SD, Giraldo P, Jeremas J, Dieterle S, Korneeva I, Liu HC, Rosenwaks Z, Witkin SS. Heat shock protein expression during gametogenesis and embryogenesis. Infect Dis Obstet Gynecol, 1999, 7:10-16
135. Niemann H. Wrenzycki C Alteration of expression of developmentally important genes in preimplantation bovine embryos by in vitro culture conditions: implications for subsequent development. Theriogeuology, 2000, 53:21-34
136. O'Dell SD, Day IN. Insulin-like growth factor Ⅱ (IGF-Ⅱ). Int J Biochem Cell Biol, 1998, 30: 767-71.
137. Ogawa H, Ono Y, Shimozawa N, Sotomaru Y, Katsuzawa Y, Hiura H, Ito M, Kono T. Disruption of imprinting in cloned mouse fetuses from embryonic stem cells. Reproduction, 2003, 126: 549-557
138. Okano M, Bell DW, Haber DA, Li E, DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development.Cell, 1999, 99:247-257
139. Okano M, Xie S, Li E. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nature Gene, 1998, 19:219-220
140. Oka Y, Waterland RA, Killian JK, Nolan CM, Jang HS, Tohara K, Sakaguchi S, Yao T, Iwashita A, Yata Y, Takahara T, Sato S, Suzuki K, Masuda T, Jirtle RL. M6P/IGF2R tumor suppressor gene mutated in hepatoceilular carcinomas in Japan. Hepatology, 2002, 35:1153-63.
141. Onishi A, Iwamoto M, Akita T, Mikawa S, Takeda K, Awata T, Hanada H, Perry AC. Pig cloning by microinjection of fetal fibroblast nuclei. Science, 2000, 289:1188-1190
142. Panchision DM, Pickel JM, Studer L, Lee SH, Turner PA, Hazel TG, McKay RD. Sequential locations of BMP reseptors control neural precursor cell production and fate. Genes Dev, 2001, 15: 2094-2110.
143. Pan GJ, Chang ZY, Scholer HR, Pei D. Stem cell pluripotency and transcription factor Oct4. Cell Res. 2002, 12:321-329
144. Parks SB, Popovich BW, Press RD. Real-time polymerase chain reaction with fluorescent hybridization probes for the detection of prevalent mutations causing common thrombophilic and iron overload phenotypes. Am J Clin Pathol, 2001, 115: 439-47.
145. Park Y, Kuroda MI.Epigenetic aspects of X-chromosome dosage compensation. Science. 2001 293:1083-5.
146. Penny GD, Kay GF, Sheardown SA, Rastan S, Brockdorff N. Requirement for Xist in the X
chromosome inactivation, Nature, 1996, 379:131-137
147. Pesce M, Sch(?)ler HR. Oct-4: Gatekeeper in the beginnings of mammalian development. Stem Cells, 2001, 19:271-278
148. Powlesland RM, Charles AK, Malik KT, Reynolds PA, Pires S, Boavida M, Brown KW. Loss of heterozygosity at 7p in Wilms' tumour development. Br J Cancer, 2000, 82: 323-9.
149. Qiao J, Bush KT, Steer DL, Stuart RO, Sakurai H, Wachsman W, Nigam SK. Multiple fibroblast growth factors support growth of the ureteric bud but have different effects on branching morphogenesis. Mech Dev, 2001, 109: 123-35.
150. Rajah R, Valentinis B, Cohen P. Insulin-like growth factor(IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-betal on programmed cell death through a p~(53)- and IGF-independent mechanism. J Biol Chem,1997, 272:12181-12188
151. Ratnam S, Mertineit C, Ding F, Howell CY, Clarke HJ, Bestor TH, Chaillet JR, Trasler JM. Dynamics of Dnmtl methyltransferase expression and intracellular localization during oogenesis and preimplantation development. Dev Biol, 2002, 245:,304-314
152. Reik W, Dean W, Walter J. Epigenetic reprogramming in mammalian development. Science, 2001, 293:1089-109
153. Ravelich SR, Breier BH, Reddy S, Keelan JA, Wells DN, James Peterson A, Lee RSE Insulin-Like Growth Factor-Ⅰ and Binding Proteins 1, 2, and 3 in Bovine Nuclear Transfer Pregnancies. Biol. Reprod, 2004, 70:430-438
154. Reynolds TS, Stevenson KR, Wathes DC. Pregnancy-specific alterations in the expression of the insulin-like growth factor system during early placental development in the ewe. Endocrinology, 1997, 138:886-897
155. Richmond EJ, Uzri A, Rogol AD. The insulin-like growth factor system in kidney diseases. Nephron, 2001, 89: 5-9.
156. Richon V M, Emiliani S, Verdin E, Webb Y, Breslow R, Rifldnd RA, Marks PA. A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc Natl Acad Sci U S A, 1998, 95:3003-7.
157. Robertson KD, Keyomarsi K, Gonzales FA, Velicescu M. Jones PA. Differential mRNA expression of the human DNA methyltransferase (DNMTS2)-1, 3a and 3b during G_0G_1 to S phase transition in normal and tumor cells. Nucleic Acids Res, 2000, 28:,2108-2113
158. Roelfsema V, Lane MH, Clark RG. Insulin-like growth factor binding protein (IGFBP) displacers: relevance to the treatment of renal disease. Pediatr Nephrol, 2000, 14: 584-8.
159. Santos F, Zakhartchenko V, Stojkovic M, Peters A, Jenuwein T, Wolf E, Reik W, Dean W. Epigenetie marking correlates with developmental potential in cloned bovine preimplantation embryos. Curr Biol, 2003, 13:1116-1121
160. Schwienbacher C, Angioni A, Scelfo R, Veronese A, Calin GA, Massazza G, Hatada Ⅰ, Barbanti-Brodano G, Negrini M. Abnormal RNA expression of 11 p15 imprinted genes and kidney developmental genes in Wilms' tumor. Cancer Res, 2000, 60:1521-5.
161. Schultz GA, Harvey MB, Watson AJ, et al. Regulation of early embryonic development by growth factors: Growth factor gene expression in cloned bovine embryos. J Animal Sci, 1996, 75: 50-57
162. Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, Yagishita N, Matsui D, Koga Y, Itoh N, Kato S. Fgf10 is essential for limb and lung formation. Nat Genet, 1999, 21: 138-141.
163. Shiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M, Winokur ST, Wasmuth JJ. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia Cell, 1994.78: 335-42.
164. Shibuya M. Structure and function of VEGF/VEGF-receptor system involved in angiogenesis. Cell Struct Funct, 2001,26: 25-
165. Shiels PG. Kind A J, Campbell KH, Waddington D, Wilmut I, Colman A, Schnieke AE. Analysis of telomere lengths in cloned sheep. Nature, 1999, 399:316-317
166. Shimasaki S. Ling N. Identification and molecular characterization of insulin-like growth factor binding proteins(IGFBP-1, -2, -3, -4, -5 and -6). Prog. Growth Factor Res. 3: 243-266, 1991
167. Shin T, K.raemer D, Pryor J, Liu L, Rugila J, Howe L, Buck S, Murphy K, Lyons L, Westhusin M. A cat cloned by nuclear transplantation. Nature, 2002, 415:859
168. Shi W. Zhao J, Anderson KD, Warburton D. Gremlin negatively modulates BMP-4 induction of embryonic mouse lung branching morphogenesis. Am J Physiol Lung Cell Mol Physiol, 2001, 280: L1030-1039.
169. Shi W, Hoeflich A, Flaswinkel H, Stojkovic M, Wolf E, Zakhartchenko V. Induction of a senescent-like phenotype does not confer the ability of bovine immortal cells to support the development of nuclear transfer embryos. Biol Reprod, 2003, 69:301-309
170. Smith SD, Soloy E, Kanka J, Holm P, Callesen H. Influence of recipient cytoplasm cell stage on transcription in bovine nucleus transfer embryos. Mol Reprod Dev, 1996, 45:444-450
171. Steiling H, Wustefeld T, Bugnon P, Brauchle M, Fassler R. Teupser D, Thiery. J, Gordon JI, Trautweiu C, Werner S. Fibroblast growth factor receptor signalling is crucial for liver homeostasis and regeneration. Oncogene, 2003, 22:4380-8
172. Stice SL, Robl JM, Ponce de Leon FA, Jerry J, Golueke PJ, Cibelli JB, Kane JJ. Cloning: new breakthroughs leading to commercial opportunities. Theriogenology, 1998, 49:129-138
173. Sun CE Lee CH, Cheng SW, Lin MH, Wu TL, Tsao KC, Chiu DT, Liou JD, Chu DC. Real-time quantitative PCR analysis for alpha-thalassemia-1 of Southeast Asian type deletion in Taiwan. Clin Genet, 2001, 60:305-9
174. Sun FL, Dean WL, Kelsey G, Allen, ND, Raik, W. Transactivation of Igf2 in a mouse model of Beckwith-Wiedemann syndrome. Nature, 1997, 389:809-815
175. Ten Have-Opbroek AA. Lung development in the mouse embryo. Exp Lung Res, 1991, 17: 111-30.
176. Tian XC, Xu J, Yang X. Normal telomere lengths found in cloned cattle. Nature Genet, 2000, 26: 272～273
177. Tsujiuchi T, Sasaki Y, Oka Y, Kuniyasu H, Konishi Y, Tsutsumi M. Alterations of the M6p/tgf2 receptor gene in hepatocellular carcinomas induced by N-nitrosodiethylamine and a choline-deficient L-amino acid-defined diet in rats. Mol Carcinog, 2004, 39:199-205
178. Tyagi S, Kramer FR. Molecular beacons: probes that fluoresce upon hybridization Nat-Biotechol, 1996, 14:303-308
179. Urist MR. Bone formation by auto induction. Science, 1965, 150:893-899
180. Vanden Veyver IB, Zoghbi HY. Methyl-CpG-binding protein 2 mutations in Rett syndrome. Curt Opin Genet Devel, 2000, 10275-279
181. Van der Vtag J, Otte AP. Transcriptional repression mediated by the human polycomb-group protein E ED involves histone deacetylation. Nat Genet, 1999, 23: 474-8
182. Van Stekelenburg-Hamers AE, Rebel HG, Van Inzen WG, de Loos FA, Drost M, Mummery CL,
Weima SM, Trounson AO. Stage-specific appearance of the mouse antigenTEC-3 innormal and nuclear transfer bovine embryos: Re-expression after nuclear transfer. Mol Reprod Dev, 1995, 37: 27～33
183. Vertino PM, Yen R-WC, Gao J, Baylin SB. De novo methylation of CpG island sequences in human fibroblasts overexpressing DNA(cysteine 5)-methyltransferase. Mol Cell Biol, 1996, 16: 4555-4565
184. Wakayama T, Perry ACF, Zuccotti M, Johnson KR, Yanagimachi R. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature, 1998, 394:369-373
185. Wakayama T, Tateno H, Mombaerts P, Yanagimachi R. Nuclear transfer into mouse zygotes. Nat Genet, 20(10, 24:108-109
186. Walburger DK, Afonina IA, Wydro R. An improved real time PCR method for simultaneous detection of C282Y and H63D mutations in the HFE gene associated with hereditary hemochromatosis. Mutat Res, 2001, 432:69-78
187. Walker NJ. Real-time and quantitative PCR: applications to mechanism-based toxicology. J Biochem Mol Toxicol, 2001, 15:121-7
188. Wall RJ, Kerr DE, Bondioli KR. Transgenic dairy cattle: genetic engineering on a large scale. J Dairy Sci, 1997, 80:2213-2224
189. Wang J, Mager J, Chert Y, Schneider E, Cross JC, Nagy A, Magnuson T.Imprinted X inactivation maintained by a mouse Polycemb group gene. Nat Genet, 2001, 28:371-5
190. Wang J, Mager J, Schnedier E, Magnuson T. The mouse PeG gene cod is required for Hox gene repression and extraembryonic development.Mature Genome, 2002, 13:493-503
191. Wang X, Li X, Willette RN, Barone FC, Feuerstein GZ. Application of real-time polymerase chain reaction to quantitate induced expression of interleukin-1 beta mRNA in ischemic brain tolerance. Neurosci Res, 2000, 59:238-46
192. MeKeehan WL, Wang F, Kan M. The heparan sulfate-fibroblast growth factor family: diversity of structure and function. Prog Nucleic Acids Res Mol Biol, 1998, 59:135-176
193. Weaver M, Dunn NR, Hogan BL. BMP4 and Fgf10 play opposing roles during lung bud morphogenesis. Development, 2000, 127:2695-2704
194. Wells DN, Misica PM, Tervit HR. Production of cloned calves following nuclear transfer with cultured adult mural granulosa cells. Biol Reprod, 1999, 60:996-1005
195. Wetteran LA, Moore MG, Lee KW, Shim ML, Cohen P. Novel aspects of the insulin-like growth factor binding proteins. Mol Genet Metab, 1999, 68:161-181
196. Wells DN, Misica PM, Tervit HR, Vivanco WH. Adult somatic cell nuclear transfer is used to preserve the last surviving cow of the Enderby Island cattle breed. Reprod Fertil Dev, 1998, 10: 369-78.
197. Wilmut I, Schnieke AE, McWhir J, Kind KL, Campbell KHS. Viable offspring derived from fetal and adult mammalian cells, Nature, 1997, 385:810-813.
198. Wilmut I. Cloning for medicine. Sci Am, 1998, 279:58-63
199. Wilmut I, Beaujean N, Somatic cell nuclear transfer. Nature, 2002, 419:583-585
200. Winger QA, Hill JR, Shin T, Watson AJ, Kraemer DC, Westhusin ME. Genetic reprogramming of lactate dehydrogenase, citrate synthase, and phosphofructokinase mRNA in bovine nuclear transfer embryos produced using bovine fibroblast cell nuclei. Mol Reprod Dev; 2000, 56: 458-464
201. Wittwer CT, Herrmann MG, Moss AA, Rasmussen RP. Continuous fluorescence monitoring of
rapid cycle DNA amplification. Biotechniques, 1997, 22:130-1,134-8
202. Wittwer CT. Ririe KM, Andrew RV. David DA, Gundry RA, Balis UJ. The LightCycler: a microvolume multisample fluorimeter with rapid temperature control. Biotechniques, 1997, 22:176-181
203. Wu J, Issa J-P, Herman J, Bassett DE, Nellkin BD, Baylin SB Expression of an exogenous eukaryotic DNA methyltransferase gene induces transformation of NIH 3T3 cells. Proc Natl Acad Sci U S A, 1993; 90:8891-8895
204 Wrenzycki C, Wells D, Herrmann D, Miller A, Oliver J, Tervit R. Niemann H. Nuclear transfer protocol affects messenger RNA expression patterns in cloned bovine blastocysts. Biol Reprod, 2001,65:309-317
205. Wrenzycki C, Lucas-Halm A, Herrmann D, Lemme E, Korsawe K, Niemann H. In vitro roduction and nuclear transfer affect dosage compensation of the X-linked gene transcripts G6PD, PGK, and Xist in preimplantation bovine embryos. Biol Reprod, 2002; 66: 127-134.
206. Xue E Tian XC, Du F, Taneja M, Dinnyes A, Dai Y, Levine H, Pereira LV, Yang X. Aberrant patterns of X chromosome inactivation in bovine clones. Nat Genet, 2002, 31:216-219.
207. Wu XR, Zao DH, Lin Q, Bu DF, Zuo CH. Rett syndrome in China: report of 9 patients. Pediatr Neurol, 1988, 4:126-127
208. Xu YQ, Grundy P, Polychronakos C. Aberrant imprinting of the insulin-like growth factor Ⅱ receptor gene in Wilms' tumor. Oncogene, 1997,14: 1041-6.
209. Yakar S. The role of circulating IGF-Ⅰ: lessons from human and animal models. Endocnne, 2002, 19:239-248
210. Yamauchi T. Yamauchi J, Kuwata T, Tamura T, Yamashita T, Bae N, Westphal H. Ozato K, Nakatani Y. Distinct but overlapping roles of historic acetylase PCAF and of the closely related PCAF-B/GCN5 in mouse embryogenesis. PNAS, 2000, 97:11303-11306.
211. Young LE, Fernandes K, McEvoy TG, Butterwith SC, Gutierrez CG, Carolan C, Broadbent PJ, Robinson JJ, Wilmut I, Sinclair KD. Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat Genet, 2001, 27:153-154
212. Young LE, Schnieke AE, McCreath K J, Wieckowski S, Konfortova G, Fernandes K, Ptak G, Kind AJ. Wilmut I, Loi P, Feil R. Conservation of IGF2-H19 and IGF2R impnnting in sheep: effects of somatic cell nuclear transfer. Mech Dev, 2003, 120:1433-1442
213. Zhao GQ. Consequences of knocking out BMP signaling in the mouse. Genesis, 2003, 35:43-56
214. Schwienbacher C, Angioni A, Scelfo R, Veronese A, Calin GA, Massazza G. Hatada I, Barbanti-Brodano G, Negrini M Abnormal RNA expression of 11 p15 imprinted genes and kidney developmental genes in Wilms' tumor. Cancer Res, 2000, 60:1521-5
215．秦鹏春，哺乳动物脴胎．北京：科学出版社，2000，397～398