Biopolym. Cell. 2004; 20(1-2):116-129.
Сучасний стан та проблеми клонування ссавців
1Морозова Л. М., 1Вагіна І. М., 1Соломко О. П.
  1. Інститут молекулярної біології і генетики НАН України
    Вул. Академіка Заболотного, 150, Київ, Україна, 03680

Abstract

Огляд присвячено аналізу літературних даних з клонування ссавців. Розглядаються проблеми, пов'язані з досягненнями й обмеженнями у плануванні ссавців: джерела донорських ядер, оптимальні фази клітинного циклу для пересаджуваних ядер, методи їхньої трансплантації, ефективність до- і постімплантаційного розвитку клонів, дефекти їхнього розвитку і зв'язок з модифікацією імпринтів.

References

[1] Evsikov S.V., Morozova L.M., Solomko A.P. Role of ooplasmic segregation in mammalian development. Roux's Archives of Developmental Biology, 1994; 203 (4):199-204.
[2] Evsikov SV, Morozova LM, Solomko AP. The role of the nucleocytoplasmic ratio in development regulation of the early mouse embryo. Development. 1990;109(2):323-8.
[3] Evsikov AV, Solomko AP. The levels and nature of translation in mouse preimplantation embryos with repressed cytokinesis. Ontogenez. 1999;30(2):103-9.
[4] Evsikov AV, Solomko AP. Changes in the cavitation start time in chimeric CB6F1 <--> BALB/c embryos. Tsitol Genet. 1998;32(3):84-7.
[5] Briggs R, King TJ. Transplantation of Living Nuclei From Blastula Cells into Enucleated Frogs' Eggs. Proc Natl Acad Sci U S A. 1952;38(5):455-63.
[6] Danielli J.F., Lorch I.J., Ord M.J., Wilson E.G. Nucleus and cytoplasm in cellular inheritance. Nature, 1955; 176 (4493):1114-1115.
[7] Bromhall JD. Nuclear transplantation in the rabbit egg. Nature. 1975;258(5537):719-22.
[8] Illmensee K, Hoppe PC. Nuclear transplantation in Mus musculus: developmental potential of nuclei from preimplantation embryos. Cell. 1981;23(1):9-18.
[9] McGrath J, Solter D. Nuclear transplantation in the mouse embryo by microsurgery and cell fusion. Science. 1983;220(4603):1300-2.
[10] Surani MA, Barton SC, Norris ML. Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature. 1984 Apr 5-11;308(5959):548-50.
[11] Tsunoda Y., Yasui T., Tokunaga T., Uchida T., Sugie T. Pronuclear transplantation in the mouse. Jap. J. Anim. Reprod. 1985; 31(3):130-134.
[12] Willadsen SM. Nuclear transplantation in sheep embryos. Nature. 1986 Mar 6-12;320(6057):63-5.
[13] Kwon OY, Kono T. Production of identical sextuplet mice by transferring metaphase nuclei from four-cell embryos. Proc Natl Acad Sci U S A. 1996;93(23):13010-3.
[14] Telford NA, Watson AJ, Schultz GA. Transition from maternal to embryonic control in early mammalian development: a comparison of several species. Mol Reprod Dev. 1990;26(1):90-100.
[15] Campbell KH, McWhir J, Ritchie WA, Wilmut I. Sheep cloned by nuclear transfer from a cultured cell line. Nature. 1996;380(6569):64-6.
[16] Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. Viable offspring derived from fetal and adult mammalian cells. Nature. 1997;385(6619):810-3.
[17] Schnieke AE, Kind AJ, Ritchie WA, Mycock K, Scott AR, Ritchie M, Wilmut I, Colman A, Campbell KH. Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science. 1997;278(5346):2130-3.
[18] Cibelli JB, Stice SL, Golueke PJ, Kane JJ, Jerry J, Blackwell C, Ponce de Le?n FA, Robl JM. Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science. 1998;280(5367):1256-8.
[19] Polejaeva IA, Chen SH, Vaught TD, Page RL, Mullins J, Ball S, Dai Y, Boone J, Walker S, Ayares DL, Colman A, Campbell KH. Cloned pigs produced by nuclear transfer from adult somatic cells. Nature. 2000;407(6800):86-90.
[20] Yang X, Jiang S, Kovacs A, Foote RH. Nuclear totipotency of cultured rabbit morulae to support full-term development following nuclear transfer. Biol Reprod. 1992;47(4):636-43.
[21] Wakayama T, Perry AC, Zuccotti M, Johnson KR, Yanagimachi R. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature. 1998;394(6691):369-74.
[22] Meng L, Ely JJ, Stouffer RL, Wolf DP. Rhesus monkeys produced by nuclear transfer. Biol Reprod. 1997;57(2):454-9.
[23] Shin T, Kraemer 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(6874):859.
[24] Woods GL, White KL, Vanderwall DK, Li GP, Aston KI, Bunch TD, Meerdo LN, Pate BJ. A mule cloned from fetal cells by nuclear transfer. Science. 2003;301(5636):1063.
[25] Dominko T, Mitalipova M, Haley B, Beyhan Z, Memili E, McKusick B, First NL. Bovine oocyte cytoplasm supports development of embryos produced by nuclear transfer of somatic cell nuclei from various mammalian species. Biol Reprod. 1999;60(6):1496-502.
[26] Campbell KH, Loi P, Otaegui PJ, Wilmut I. Cell cycle co-ordination in embryo cloning by nuclear transfer. Rev Reprod. 1996;1(1):40-6.
[27] Campbell KH, Ritchie WA, Wilmut I. Nuclear-cytoplasmic interactions during the first cell cycle of nuclear transfer reconstructed bovine embryos: implications for deoxyribonucleic acid replication and development. Biol Reprod. 1993;49(5):933-42.
[28] McGrath J, Solter D. Inability of mouse blastomere nuclei transferred to enucleated zygotes to support development in vitro. Science. 1984;226(4680):1317-9.
[29] Cheong HT, Takahashi Y, Kanagawa H. Birth of mice after transplantation of early cell-cycle-stage embryonic nuclei into enucleated oocytes. Biol Reprod. 1993;48(5):958-63.
[30] Nurse P. Universal control mechanism regulating onset of M-phase. Nature. 1990;344(6266):503-8.
[31] Solter D. Mammalian cloning: advances and limitations. Nat Rev Genet. 2000;1(3):199-207.
[32] Kim JM, Ogura A, Nagata M, Aoki F. Analysis of the mechanism for chromatin remodeling in embryos reconstructed by somatic nuclear transfer. Biol Reprod. 2002;67(3):760-6.
[33] Wassarman PM, Litscher ES. Towards the molecular basis of sperm and egg interaction during mammalian fertilization. Cells Tissues Organs. 2001;168(1-2):36-45.
[34] Kirkman-Brown JC, Sutton KA, Florman HM. How to attract a sperm. Nat Cell Biol. 2003;5(2):93-6.
[35] Arney KL, Bao S, Bannister AJ, Kouzarides T, Surani MA. Histone methylation defines epigenetic asymmetry in the mouse zygote. Int J Dev Biol. 2002;46(3):317-20.
[36] Kikyo N, Wade PA, Guschin D, Ge H, Wolffe AP. Active remodeling of somatic nuclei in egg cytoplasm by the nucleosomal ATPase ISWI. Science. 2000;289(5488):2360-2.
[37] Modlinski JA, Karasiewicz J. Somatic cloning in mammals. Med Wieku Rozwoj. 2001;5(1 Suppl 1):9-25.
[38] Ono Y, Shimozawa N, Muguruma K, Kimoto S, Hioki K, Tachibana M, Shinkai Y, Ito M, Kono T. Production of cloned mice from embryonic stem cells arrested at metaphase. Reproduction. 2001;122(5):731-6.
[39] Wakayama T, Rodriguez I, Perry AC, Yanagimachi R, Mombaerts P. Mice cloned from embryonic stem cells. Proc Natl Acad Sci U S A. 1999;96(26):14984-9.
[40] Yamazaki Y, Makino H, Hamaguchi-Hamada K, Hamada S, Sugino H, Kawase E, Miyata T, Ogawa M, Yanagimachi R, Yagi T. Assessment of the developmental totipotency of neural cells in the cerebral cortex of mouse embryo by nuclear transfer. Proc Natl Acad Sci U S A. 2001;98(24):14022-6.
[41] Ogura A, Inoue K, Ogonuki N, Noguchi A, Takano K, Nagano R, Suzuki O, Lee J, Ishino F, Matsuda J. Production of male cloned mice from fresh, cultured, and cryopreserved immature Sertoli cells. Biol Reprod. 2000;62(6):1579-84.
[42] Sato K, Hosaka K, Ohi S, Uchiyama H, Tokieda Y, Ishiwata I. Mouse fetuses by nuclear transfer from embryonic stem cells. Hum Cell. 2000;13(4):197-202.
[43] McCreath KJ, Howcroft J, Campbell KH, Colman A, Schnieke AE, Kind AJ. Production of gene-targeted sheep by nuclear transfer from cultured somatic cells. Nature. 2000;405(6790):1066-9.
[44] 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(5396):2095-8.
[45] 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(3):990-5.
[46] Lanza RP, Cibelli JB, Blackwell C, Cristofalo VJ, Francis MK, Baerlocher 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(5466):665-9.
[47] 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(5482):1188-90.
[48] Wakayama T, Yanagimachi R. Cloning of male mice from adult tail-tip cells. Nat Genet. 1999;22(2):127-8.
[49] Rideout WM 3rd, Wakayama T, Wutz A, Eggan K, Jackson-Grusby L, Dausman J, Yanagimachi R, Jaenisch R. Generation of mice from wild-type and targeted ES cells by nuclear cloning. Nat Genet. 2000;24(2):109-10.
[50] Keefer CL, Baldassarre H, Keyston R, Wang B, Bhatia B, Bilodeau AS, Zhou JF, Leduc M, Downey BR, Lazaris A, Karatzas CN. Generation of dwarf goat (Capra hircus) clones following nuclear transfer with transfected and nontransfected fetal fibroblasts and in vitro-matured oocytes. Biol Reprod. 2001;64(3):849-56.
[51] Kang YK, Koo DB, Park JS, Choi YH, Lee KK, Han YM. Influence of oocyte nuclei on demethylation of donor genome in cloned bovine embryos. FEBS Lett. 2001;499(1-2):55-8.
[52] Wells DN, Misica PM, Day TA, Tervit HR. Production of cloned lambs from an established embryonic cell line: a comparison between in vivo- and in vitro-matured cytoplasts. Biol Reprod. 1997;57(2):385-93.
[53] Eggan K, Akutsu H, Loring J, Jackson-Grusby L, Klemm M, Rideout WM 3rd, Yanagimachi R, Jaenisch R. Hybrid vigor, fetal overgrowth, and viability of mice derived by nuclear cloning and tetraploid embryo complementation. Proc Natl Acad Sci U S A. 2001;98(11):6209-14.
[54] Rideout WM 3rd, Eggan K, Jaenisch R. Nuclear cloning and epigenetic reprogramming of the genome. Science. 2001;293(5532):1093-8.
[55] Babinet C, Cohen-Tannoudji M. Genome engineering via homologous recombination in mouse embryonic stem (ES) cells: an amazingly versatile tool for the study of mammalian biology. An Acad Bras Cienc. 2001;73(3):365-83.
[56] Tsunoda Y, Kato Y. Nuclear transplantation of embryonic stem cells in mice. J Reprod Fertil. 1993;98(2):537-40.
[57] Illmensee K. Transplantation of embryonic nuclei into unfertilized eggs of Drosophila melanogaster. Nature. 1968;219(5160):1268-9.
[58] Wakayama T , Yanagimachi R. Mouse cloning with nucleus donor cells of different age and type. Mol Reprod Dev. 2001;58(4):376-83.
[59] Renard JP, Chastant S, Chesne P, Richard C, Marchal J, Cordonnier N, Chavatte P, Vignon X. Lymphoid hypoplasia and somatic cloning. Lancet. 1999;353(9163):1489-91.
[60] Tamashiro KL, Wakayama T, Blanchard RJ, Blanchard DC, Yanagimachi R. Postnatal growth and behavioral development of mice cloned from adult cumulus cells. Biol Reprod. 2000;63(1):328-34.
[61] Tamashiro KL, Wakayama T, Akutsu H, Yamazaki Y, Lachey JL, Wortman MD, Seeley RJ, D'Alessio DA, Woods SC, Yanagimachi R, Sakai RR. Cloned mice have an obese phenotype not transmitted to their offspring. Nat Med. 2002;8(3):262-7.
[62] Wakayama T, Shinkai Y, Tamashiro KL, Niida H, Blanchard DC, Blanchard RJ, Ogura A, Tanemura K, Tachibana M, Perry AC, Colgan DF, Mombaerts P, Yanagimachi R. Cloning of mice to six generations. Nature. 2000;407(6802):318-9.
[63] 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(5548):1893-4.
[64] Giles RE, Blanc H, Cann HM, Wallace DC. Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci U S A. 1980;77(11):6715-9.
[65] Kaneda H, Hayashi J, Takahama S, Taya C, Lindahl KF, Yonekawa H. Elimination of paternal mitochondrial DNA in intraspecific crosses during early mouse embryogenesis. Proc Natl Acad Sci U S A. 1995;92(10):4542-6.
[66] Ankel-Simons F, Cummins JM. Misconceptions about mitochondria and mammalian fertilization: implications for theories on human evolution. Proc Natl Acad Sci U S A. 1996;93(24):13859-63.
[67] Piko L, Taylor KD. Amounts of mitochondrial DNA and abundance of some mitochondrial gene transcripts in early mouse embryos. Dev Biol. 1987;123(2):364-74.
[68] King MP, Attardi G. Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science. 1989;246(4929):500-3.
[69] Evans MJ, Gurer C, Loike JD, Wilmut I, Schnieke AE, Schon EA. Mitochondrial DNA genotypes in nuclear transfer-derived cloned sheep. Nat Genet. 1999;23(1):90-3.
[70] Meirelles FV, Smith LC. Mitochondrial genotype segregation during preimplantation development in mouse heteroplasmic embryos. Genetics. 1998;148(2):877-83.
[71] Jenuth JP, Peterson AC, Shoubridge EA. Tissue-specific selection for different mtDNA genotypes in heteroplasmic mice. Nat Genet. 1997;16(1):93-5.
[72] Steinborn R, Schinogl P, Zakhartchenko V, Achmann R, Schernthaner W, Stojkovic M, Wolf E, M?ller M, Brem G. Mitochondrial DNA heteroplasmy in cloned cattle produced by fetal and adult cell cloning. Nat Genet. 2000;25(3):255-7.
[73] Steinborn R, Zakhartchenko V, Jelyazkov J, Klein D, Wolf E, Muller M, Brem G. Composition of parental mitochondrial DNA in cloned bovine embryos. FEBS Lett. 1998;426(3):352-6.
[74] Steinborn R, Zakhartchenko V, Wolf E, Muller M, Brem G. Non-balanced mix of mitochondrial DNA in cloned cattle produced by cytoplast-blastomere fusion. FEBS Lett. 1998;426(3):357-61.
[75] Blackburn EH. Structure and function of telomeres. Nature. 1991;350(6319):569-73.
[76] van Steensel B, de Lange T. Control of telomere length by the human telomeric protein TRF1. Nature. 1997;385(6618):740-3.
[77] Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green DK, Allshire RC. Telomere reduction in human colorectal carcinoma and with ageing. Nature. 1990;346(6287):866-8.
[78] Morin GB. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell. 1989;59(3):521-9.
[79] Counter CM, Hahn WC, Wei W, Caddle SD, Beijersbergen RL, Lansdorp PM, Sedivy JM, Weinberg RA. Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization. Proc Natl Acad Sci U S A. 1998;95(25):14723-8.
[80] Tian XC, Xu J, Yang X. Normal telomere lengths found in cloned cattle. Nat Genet. 2000;26(3):272-3.
[81] Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345(6274):458-60.
[82] Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, Greider CW. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell. 1997;91(1):25-34.
[83] Shiels PG, Kind AJ, Campbell KH, Waddington D, Wilmut I, Colman A, Schnieke AE. Analysis of telomere lengths in cloned sheep. Nature. 1999;399(6734):316-7.
[84] Mitalipov SM, Wolf DP. Mammalian cloning: possibilities and threats. Ann Med. 2000;32(7):462-8.
[85] Vogel G. In contrast to Dolly, cloning resets telomere clock in cattle. Science. 2000;288(5466):586-7.
[86] Betts D, Bordignon V, Hill J, Winger Q, Westhusin M, Smith L, King W. Reprogramming of telomerase activity and rebuilding of telomere length in cloned cattle. Proc Natl Acad Sci U S A. 2001;98(3):1077-82.
[87] Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998;279(5349):349-52.
[88] Kipling D, Cooke HJ. Hypervariable ultra-long telomeres in mice. Nature. 1990;347(6291):400-2.
[89] Prowse KR, Greider CW. Developmental and tissue-specific regulation of mouse telomerase and telomere length. Proc Natl Acad Sci U S A. 1995;92(11):4818-22.
[90] Solter D. Imprinting. Int J Dev Biol. 1998;42(7):951-4.
[91] Koniukhov BV, Platonov ES. Genomic imprinting in mammals. Genetika. 2001 37(1):5-17.
[92] Reik W, Walter J. Evolution of imprinting mechanisms: the battle of the sexes begins in the zygote. Nat Genet. 2001;27(3):255-6.
[93] Reik W., Surani A.M. Genomic Imprinting, 1997 209, Oxford: Oxford Univ. press p. 245.
[94] Falls JG, Pulford DJ, Wylie AA, Jirtle RL. Genomic imprinting: implications for human disease. Am J Pathol. 1999;154(3):635-47.
[95] Lerchner W, Barlow DP. Paternal repression of the imprinted mouse Igf2r locus occurs during implantation and is stable in all tissues of the post-implantation mouse embryo. Mech Dev. 1997;61(1-2):141-9.
[96] Guillemot F, Caspary T, Tilghman SM, Copeland NG, Gilbert DJ, Jenkins NA, Anderson DJ, Joyner AL, Rossant J, Nagy A. Genomic imprinting of Mash2, a mouse gene required for trophoblast development. Nat Genet. 1995;9(3):235-42.
[97] Giddings SJ, King CD, Harman KW, Flood JF, Carnaghi LR. Allele specific inactivation of insulin 1 and 2, in the mouse yolk sac, indicates imprinting. Nat Genet. 1994;6(3):310-3.
[98] Szabo PE, Mann JR. Allele-specific expression and total expression levels of imprinted genes during early mouse development: implications for imprinting mechanisms. Genes Dev. 1995;9(24):3097-108.
[99] Tremblay KD, Saam JR, Ingram RS, Tilghman SM, Bartolomei MS. A paternal-specific methylation imprint marks the alleles of the mouse H19 gene. Nat Genet. 1995;9(4):407-13.
[100] DeChiara TM, Robertson EJ, Efstratiadis A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell. 1991;64(4):849-59.
[101] Brockdorff N, Ashworth A, Kay GF, Cooper P, Smith S, McCabe VM, Norris DP, Penny GD, Patel D, Rastan S. Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome. Nature. 1991;351(6324):329-31.
[102] Takagi N, Sasaki M. Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse. Nature. 1975;256(5519):640-2.
[103] Szabo PE, Pfeifer GP, Mann JR. Characterization of novel parent-specific epigenetic modifications upstream of the imprinted mouse H19 gene. Mol Cell Biol. 1998;18(11):6767-76.
[104] Caspary T, Cleary MA, Baker CC, Guan XJ, Tilghman SM. Multiple mechanisms regulate imprinting of the mouse distal chromosome 7 gene cluster. Mol Cell Biol. 1998;18(6):3466-74.
[105] Kato Y, Rideout WM 3rd, Hilton K, Barton SC, Tsunoda Y, Surani MA. Developmental potential of mouse primordial germ cells. Development. 1999;126(9):1823-32.
[106] Kono T, Obata Y, Yoshimzu T, Nakahara T, Carroll J. Epigenetic modifications during oocyte growth correlates with extended parthenogenetic development in the mouse. Nat Genet. 1996;13(1):91-4.
[107] Lee J, Inoue K, Ono R, Ogonuki N, Kohda T, Kaneko-Ishino T, Ogura A, Ishino F. Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells. Development. 2002;129(8):1807-17.
[108] Howlett SK, Reik W. Methylation levels of maternal and paternal genomes during preimplantation development. Development. 1991;113(1):119-27.
[109] Oswald J, Engemann S, Lane N, Mayer W, Olek A, Fundele R, Dean W, Reik W, Walter J. Active demethylation of the paternal genome in the mouse zygote. Curr Biol. 2000;10(8):475-8.
[110] Mayer W, Niveleau A, Walter J, Fundele R, Haaf T. Demethylation of the zygotic paternal genome. Nature. 2000;403(6769):501-2.
[111] Olek A, Walter J. The pre-implantation ontogeny of the H19 methylation imprint. Nat Genet. 1997;17(3):275-6.
[112] Morison IM, Reeve AE. A catalogue of imprinted genes and parent-of-origin effects in humans and animals. Hum Mol Genet. 1998;7(10):1599-609.
[113] Kim JM, Ogura A, Nagata M, Aoki F. Analysis of the mechanism for chromatin remodeling in embryos reconstructed by somatic nuclear transfer. Biol Reprod. 2002;67(3):760-6.
[114] Latham KE , Garrels JI, Solter D. Alterations in protein synthesis following transplantation of mouse 8-cell stage nuclei to enucleated 1-cell embryos. Dev Biol. 1994;163(2):341-50.
[115] Latham KE, Solter D, Schultz RM. Activation of a two-cell stage-specific gene following transfer of heterologous nuclei into enucleated mouse embryos. Mol Reprod Dev. 1991;30(3):182-6.
[116] Kang YK, Koo DB, Park JS, Choi YH, Chung AS, Lee KK, Han YM. Aberrant methylation of donor genome in cloned bovine embryos. Nat Genet. 2001;28(2):173-7.
[117] Ohgane J, Wakayama T, Kogo Y, Senda S, Hattori N, Tanaka S, Yanagimachi R, Shiota K. DNA methylation variation in cloned mice. Genesis. 2001;30(2):45-50.
[118] 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(2):153-4.
[119] Young L.E., Gutierrez C.G., Butterviilh S.C., Robinson J.J., Broadbent P.J., McEvoy T.G., Wilmut I., Sinclair, K.D. Altered IGF binding protein expression is associated with large offspring syndrome in fetal sheep. Theriogenoiogy. 1999; 51(1):196.
[120] Eggan K, Akutsu H, Hochedlinger K, Rideout W 3rd, Yanagimachi R, Jaenisch R. X-Chromosome inactivation in cloned mouse embryos. Science. 2000;290(5496):1578-81.
[121] Humpherys D, Eggan K, Akutsu H, Hochedlinger K, Rideout WM 3rd, Biniszkiewicz D, Yanagimachi R, Jaenisch R. Epigenetic instability in ES cells and cloned mice. Science. 2001;293(5527):95-7.
[122] Doherty AS, Mann MR, Tremblay KD, Bartolomei MS, Schultz RM. Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo. Biol Reprod. 2000;62(6):1526-35.
[123] Khosla S, Dean W, Brown D, Reik W, Feil R. Culture of preimplantation mouse embryos affects fetal development and the expression of imprinted genes. Biol Reprod. 2001;64(3):918-26.
[124] Jones BK, Levorse J, Tilghman SM. Deletion of a nuclease-sensitive region between the Igf2 and H19 genes leads to Igf2 misregulation and increased adiposity. Hum Mol Genet. 2001;10(8):807-14.
[125] Dean W, Bowden L, Aitchison A, Klose J, Moore T, Meneses JJ, Reik W, Feil R. Altered imprinted gene methylation and expression in completely ES cell-derived mouse fetuses: association with aberrant phenotypes. Development. 1998;125(12):2273-82.
[126] Brophy B, Smolenski G, Wheeler T, Wells D, L'Huillier P, Laible G. Cloned transgenic cattle produce milk with higher levels of beta-casein and kappa-casein. Nat Biotechnol. 2003;21(2):157-62.
[127] Bulfield G. Farm animal biotechnology. Trends Biotechnol. 2000;18(1):10-3.
[128] Wolf DP, Meng L, Ouhibi N, Zelinski-Wooten M. Nuclear transfer in the rhesus monkey: practical and basic implications. Biol Reprod. 1999;60(2):199-204.
[129] Gonos ES. Genetics of aging: lessons from centenarians. Exp Gerontol. 2000;35(1):15-21.
[130] Illmensee K. Cloning in reproductive medicine. J Assist Reprod Genet. 2001;18(8):451-67.