Nuclear Remodeling and Nuclear Reprogramming for Making Transgenic Pigs by Nuclear Transfer

  • Randall S. Prather
Part of the Advances in Experimental Medicine and Biology book series (volume 591)


A better understanding of the cellular and molecular events that occur when a nucleus is transferred to the cytoplasm of an oocyte will permit the development of improved procedures for performing nuclear transfer and cloning. In some cases it appears that the gene(s) are reprogrammed, while in other cases there appears to be little effect on gene expression. Not only does the pattern of gene expression need to be reprogrammed, but other structures within the nucleus also need to be remodeled. While nuclear transfer works and transgenic and knockout animals can be created, it still is an inefficient process. However, even with the current low efficiencies this technique has proved very valuable for the production of animals that might be useful for tissue or organ transplantation to humans.


Telomere Length Nuclear Transfer Blastocyst Stage Somatic Cell Nuclear Transfer Linker Histone 
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  1. 1.
    Spemann H. Embryonic Development and Induction. New York: Hafner, 1938:210–211.Google Scholar
  2. 2.
    Briggs R, King TJ. Transplantation of living cell nuclei from blastula cells into enucleated frogs’ eggs. Proc Natl Acad Sci USA 1952; 38:455–463.PubMedCrossRefGoogle Scholar
  3. 3.
    Gurdon JB. Nuclear transplantation in eggs and oocytes. J Cell Sci 1986; (Suppl 4):287–318.Google Scholar
  4. 4.
    Prather RS, First NL. Cloning embryos by nuclear transfer. J Reprod Fertility 1990; (Suppl 41):125–134.Google Scholar
  5. 5.
    First NL, Prather RS. Genomic potential in mammals. Differentiation 1991; 48:1–8.PubMedGoogle Scholar
  6. 6.
    Illmensee K, Hoppe PC. Nuclear transplantation in Mus musculus: Developmental potential of nuclei from preimplantation embryos. Cell 1981; 23:9–18.PubMedCrossRefGoogle Scholar
  7. 7.
    McGrath J, Solter D. Inability of mouse blastomere nuclei transferred to enucleated zygotes to support development in vitro. Science 1983; 226:1317–1319.CrossRefGoogle Scholar
  8. 8.
    Willadsen SM. Nuclear transplantation in sheep embryos. Nature 1986; 31:956–962.Google Scholar
  9. 9.
    Prather RS, Barnes FL, Sims ML et al. Nuclear transfer in the bovine embryo: Assessment of donor nuclei and recipient oocyte. Biol Reprod 1987; 37:859–866.PubMedCrossRefGoogle Scholar
  10. 10.
    Stice SL, Robl JM. Nuclear reprogramming in nuclear transplant rabbit embryos. Biol Reprod 1988; 39:657–664.PubMedCrossRefGoogle Scholar
  11. 11.
    Prather RS, Sims MM, First NL. Nuclear transplantation in early pig embryos. Biol Reprod 1989; 41:414–418.PubMedCrossRefGoogle Scholar
  12. 12.
    Sims M, First NL. Production of calves by transfer of nuclei from cultured inner cell mass cells. Proc Natl Acad Sci USA 1994; 91(13):6143–6147.PubMedCrossRefGoogle Scholar
  13. 13.
    Campbell KHS, McWhir J, Ritchie WA et al. Sheep cloned by nuclear transfer from a cultured cell line. Nature 1996; 380(6569):64–66.PubMedCrossRefGoogle Scholar
  14. 14.
    Polejaeva IA, Chen SH, Vaught TD et al. Cloned pigs produced by nuclear transfer from adult somatic cells. Nature 2000; 407(6800):86–90.PubMedCrossRefGoogle Scholar
  15. 15.
    Park KW, Cheong HT, Lai LX et al. Production of nuclear transfer-derived swine that express the enhanced green fluorescent protein. Anim Biotechnol 2001; 12(2):173–181.PubMedCrossRefGoogle Scholar
  16. 16.
    Prather RS, Sims MM, First NL. Nuclear transplantation in the pig embryo: Nuclear swelling. J Exp Zool 1990; 255:355–358.PubMedCrossRefGoogle Scholar
  17. 17.
    Prather RS, Sims MM, Maul GG et al. Nuclear lamin antigens are developmentally regulated during porcine and bovine embryogenesis. Biol Reprod 1989; 41:123–132.PubMedCrossRefGoogle Scholar
  18. 18.
    Prather RS, Rickords LF. Developmental regulation of a snRNP core protein epitope during pig embryogenesis and after nuclear transfer for cloning. Mol Reprod Dev 1992; 33:119–123.PubMedCrossRefGoogle Scholar
  19. 19.
    Mayes MA, Stogsdill PL, Parry TW et al. Reprogramming of nudeoli after nuclear transfer of pig blastomeres into enucleated oocytes. Dev Biol 1994; 163:542.Google Scholar
  20. 20.
    Parry TW, Prather RS. Carry-over of mRNA during nuclear transfer in pigs. Reproduction, Nutrition, Development 1995; 35(3):313–318.PubMedCrossRefGoogle Scholar
  21. 21.
    Liu ZH, Hao YH, Lai LX et al. Morphology and dynamics of alpha-tubulin and nuclear mitotic apparatus protein during the first cell cycle in porcine nuclear transfer embryos, parthenogenetic embryos and in vitro fertilization embryos. Biol Reprod 2004; (Special Issue):215.Google Scholar
  22. 22.
    Teranishi T, Tanaka M, Kimoto S et al. Rapid replacement of somatic linker histones with the oocyte-specific linker histone H1 foo in nuclear transfer. Dev Biol 2004; 266(1):76–86.PubMedCrossRefGoogle Scholar
  23. 23.
    Gao SR, Chung YG, Parseghian MH et al. Rapid H1 linker histone transitions following fertilization or somatic cell nuclear transfer: Evidence for a uniform developmental program in mice. Dev Biol 2004; 266(1):62–75.PubMedCrossRefGoogle Scholar
  24. 24.
    Bordignon V, Clarke HJ, Smith LC. Factors controlling the loss of immunoreactive somatic histone H1 from blastomere nuclei in oocyte cytoplasm: A potential marker of nuclear reprogramming. Dev Biol 2001; 233(1):192–203.PubMedCrossRefGoogle Scholar
  25. 25.
    Moore SC, Jason L, Ausio J. The elusive structural role of ubiquitinated histones [Review]. Biochemistry and Cell Biology-Biochimie and Biologie Cellulaire 2002; 80(3):311–319.CrossRefGoogle Scholar
  26. 26.
    Baarends WM, Hoogerbrugge TW, Roest HP et al. Histone ubiquitination and chromatin remodeling in mouse spermatogenesis. Dev Biol 1999; 207(2):322–333.PubMedCrossRefGoogle Scholar
  27. 27.
    Chen HY, Sun JM, Zhang Y et al. Ubiquitination of histone H3 in elongating spermatids of rat testes. J Biol Chem 1998; 273(21):13165–13169.PubMedCrossRefGoogle Scholar
  28. 28.
    Tovich PR, Oko RJ. Somatic histones are components of the perinuclear theca in bovine spermatozoa. J Biol Chem 2003; 278(34):32431–32438.PubMedCrossRefGoogle Scholar
  29. 29.
    Prather RS, Sutovsky P, Green JA. Nuclear remodeling and reprogramming in transgenic pig production. Proc Soc Exp Biol Med 2004; 229:1120–1126.Google Scholar
  30. 30.
    Shiels PG, Kind AJ, Campbell KHS et al. Analysis of telomere lengths in cloned sheep. Nature 1999; 399(6734):316–317.PubMedCrossRefGoogle Scholar
  31. 31.
    Tian XC, Xu J, Yang XZ. Normal telomere lengths found in cloned cattle. Nat Genet 2000; 26(3):272–273.PubMedCrossRefGoogle Scholar
  32. 32.
    Miyashita N, Shiga K, Fujita T et al. Normal telomere lengths of spermatozoa in somatic cell-cloned bulls. Theriogenology 2003; 59(7):1557–1565.PubMedCrossRefGoogle Scholar
  33. 33.
    Lanza RP, Cibelli JB, Blackwell C et al. Extension of cell life-span and telomere length in animals cloned from senescent somatic cells. Science 2000; 288(5466):665–669.PubMedCrossRefGoogle Scholar
  34. 34.
    Miyashita N, Shiga K, Yonai M et al. Remarkable differences in telomere lengths among cloned cattle derived from different cell types. Biol Reprod 2002; 66(6):1649–1655.PubMedCrossRefGoogle Scholar
  35. 35.
    Le JA, Carter DB, Xu J et al. Telomere lengths in cloned transgenic pigs. Biol Reprod 2004; 70:1589–1593.CrossRefGoogle Scholar
  36. 36.
    Kang YK. 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(43):39980–39984.PubMedCrossRefGoogle Scholar
  37. 37.
    Kang YK, Yeo S, Kim SH et al. Precise recapitulation of methylation change in early cloned embryos. Mol Reprod Dev 2003; 66(1):32–37.PubMedCrossRefGoogle Scholar
  38. 38.
    Kang YK, Koo DB, Park JS et al. Aberrant methylation of donor genome in cloned bovine embryos. Nat Genet 2001; 28(2):173–177.PubMedCrossRefGoogle Scholar
  39. 39.
    Kang YK. Influence of oocyte nuclei on demethylation of donor genome in cloned bovine embryos. FEBS Letters 2001; 499(1–2):55–58.PubMedCrossRefGoogle Scholar
  40. 40.
    Winger QA, Hill JR, Shin TY et al. 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(4):458–464.PubMedCrossRefGoogle Scholar
  41. 41.
    Park KW, Kuhholzer B, Lai LX et al. Development and expression of the green fluorescent protein in porcine embryos derived from nuclear transfer of transgenic granulosa-derived cells. Anim Reprod Sci 2001; 68(1–2):111–120.PubMedCrossRefGoogle Scholar
  42. 42.
    Park KW, Lai LX, Cheong HT et al. Mosaic gene expression in nuclear transfer-derived embryos and the production of cloned transgenic pigs from ear-derived fibroblasts. Biol Reprod 2002; 66(4):1001–1005.PubMedCrossRefGoogle Scholar
  43. 43.
    DeSousa PA, Winger Q, Hill JR et al. Reprogramming of fibroblast nuclei after transfer into bovine oocytes. Cloning 1999; 1:63–69.CrossRefGoogle Scholar
  44. 44.
    Daniels R, Hall V, Trounson AO. Analysis of gene transcription in bovine nuclear transfer embryos reconstructed with granulosa cell nuclei. Biol Reprod 2000; 63(4):1034–1040.PubMedCrossRefGoogle Scholar
  45. 45.
    Daniels R, Hall VJ, French AJ et al. Comparison of gene transcription in cloned bovine embryos produced by different nuclear transfer techniques. Mol Reprod Dev 2001; 60(3):281–288.PubMedCrossRefGoogle Scholar
  46. 46.
    Humphreys D, Eggan K, Akutsu H et al. Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei. Proc Natl Acad Sci USA 2002; 99(20):12889–12894.CrossRefGoogle Scholar
  47. 47.
    Lee SH, Kim DY, Nam DH et al. Role of messenger RNA expression of platelet-activating factor and its receptor in porcine in vitro-fertilized and cloned embryo development. Biol Reprod 2004.Google Scholar
  48. 48.
    Zhu H, Craig JA, Dyce PW et al. Embryos derived from porcine skin-derived stem cells exhibit enhanced preimplantation development. Biol Reprod 2004; 71(6):1890–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Hao YH, Lai LX, Mao JD et al. Apoptosis and in vitro development of preimplantation porcine embryos derived in vitro or by nuclear transfer. Biol Reprod 2003; 69(2):501–507.PubMedCrossRefGoogle Scholar
  50. 50.
    Eggan E, Baldwin K, Tackett M et al. Mice cloned from olfactory sensory neurons. Nature 2004; 428(6978):44–49.PubMedCrossRefGoogle Scholar
  51. 51.
    Li JS, Ishii T, Feinstein P et al. Odorant receptor gene choice is reset by nuclear transfer from mouse olfactory sensory neurons. Nature 2004; 428(6981):393–399.PubMedCrossRefGoogle Scholar
  52. 52.
    Hochedlinger K, Jaenisch R. Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature 2002; 415(6875):1035–1038.PubMedCrossRefGoogle Scholar
  53. 53.
    Hochedlinger K, Blelloch R, Brennan C et al. Reprogramming of a melanoma genome by nuclear transplantation. Genes Dev 2004; 18(15):1875–1885.PubMedCrossRefGoogle Scholar
  54. 54.
    Li L, Connelly MC, Wetmore C et al. Mouse embryos cloned from brain tumors. Cancer Res 2003; 63(11):2733–2736.PubMedGoogle Scholar
  55. 55.
    Whitworth K, Springer GK, Forrester LJ et al. Developmental expression of 2,489 genes during pig embryogenesis: An EST project. Biol Reprod 2004; 71:1230–1243.PubMedCrossRefGoogle Scholar
  56. 56.
    Whitworth KM, Agca C, Kim JG et al. Transcriptional profiling of pig embryogenesis by using a 15k member unigene set specific for pig reprodutive tissues and embryos, and embryos. Biol Reprod 2005; 72(6):1437–51.PubMedCrossRefGoogle Scholar
  57. 57.
    Krause WJ, Charlson EJ, Sherman DM et al. Three-dimensional reconstruction of mitochondrial aggregates in porcine oocytes, zygotes and early embryos using a personal computer. Zoologischer Anzeiger 1992; 229:21–36.Google Scholar
  58. 58.
    Hyttel P, Niemann H. Ultrastructure of pocrine embryos following development in vitro versus in vivo. Mol Reprod Dev 1990; 27:136–144.PubMedCrossRefGoogle Scholar
  59. 59.
    Jolliff WJ, Prather RS. Parthenogenic development of in vitro-matured, in vivo-cultured porcine oocytes beyond blastocyst. Biol Reprod 1997; 56(2):544–548.PubMedCrossRefGoogle Scholar
  60. 60.
    Smith LC, Alcivar AA. Cytoplasmic inheritance and its effects on development and performance. J Reprod Fertility 1993; (Suppl 48):31–43.Google Scholar
  61. 61.
    Meirelles FV, Smith LC. Mitochondrial genotype segregation in a mouse heteroplasmic lineage produced by embryonic karyoplast transplantation. Genetics 1997; 145(2):445–451.PubMedGoogle Scholar
  62. 62.
    Meirelles FV, Smith LC. Mitochondrial genotype segregation during preimplantation development in mouse heteroplasmic embryos. Genetics 1998; 148(2):877–883.PubMedGoogle Scholar
  63. 63.
    Smith LC, Bordignon V, Garcia JM et al. Mitochondrial genotype segregation and effects during mammalian development: Applications to biotechnology. Theriogenology 2000; 53(1):35–46.PubMedCrossRefGoogle Scholar
  64. 64.
    Meirelles FV, Bordignon V, Watanabe Y et al. Complete replacement of the mitochondrial genotype in a Bos indicus calf reconstructed by nuclear transfer to a Bos taurus oocyte. Genetics 2001; 158(1):351–356.PubMedGoogle Scholar
  65. 65.
    Schatten G. The centrosome and its mode of inheritance-the reduction of the centrosome during gametogenesis and its restoration during fertilization. Dev Biol 1994; 165(2):299–335.PubMedCrossRefGoogle Scholar
  66. 66.
    Mananadhar G, Schatten H, Lai L et al. Centrosomal protein centrin is not detectable during early cleavages but reappears during late blastocyst stage in porcine embryos. Biol Reprod 2004; (Special Issue):146.Google Scholar
  67. 67.
    Sutovsky P, Manandhar G, Laurincik J et al. Expression and proteasomal degradation of the Major Vault Protein (MVP) in mammalian oocytes and zygotes. Reproduction 2005; 129(3):269–82.PubMedCrossRefGoogle Scholar
  68. 68.
    Walker SK, Hartwich KM, Seamark RF. The production of unusually large offspring following embryo manipulation-Concepts and challenges. Theriogenology 1996; 45(1):111–120.CrossRefGoogle Scholar
  69. 69.
    Wilson JM, Williams JD, Bondioli KR et al. Comparison of birth weight and growth characteristics of bovine calves produced by nuclear transfer (Cloning), embryo transfer and natural mating. Anim Reprod Sci 1995; 38(1–2):73–83.CrossRefGoogle Scholar
  70. 70.
    Carter DB, Lai L, Park KW et al. Phenotyping of transgenic cloned pigs. Cloning and Stem Cells 2002; 4:131–145.PubMedCrossRefGoogle Scholar
  71. 71.
    Carroll JA, Carter DB, Korte SW et al. Evaluation of the acute phase response in cloned pigs following a lipopolysaccharide challenge. Domest Anim Endocrinol 2005; 29(3):564–72PubMedCrossRefGoogle Scholar
  72. 72.
    Cabot RA, Kuhholzer B, Chan AWS et al. Transgenic pigs produced using in vitro matured oocytes infected with a retroviral vector. Anim Biotechnol 2001; 12(2):205–214.PubMedCrossRefGoogle Scholar
  73. 73.
    Conway KL. Birth weight of bovine calves produced by nuclear transfer (cloning) and their off-spring (embryo transfer). Dissertation Abstracts International 1996; 57-06 (B):3462.Google Scholar
  74. 74.
    Tamashiro KLK, Wakayama T, Akutsu H et al. Cloned mice have an obese phenotype not transmitted to their offspring. Nature Medicine 2002; 8(3):262–267.PubMedCrossRefGoogle Scholar
  75. 75.
    Kolber-Simonds D, Lai L, Watt SR et al. Alpha-1,3-galactosyltransferase null pigs via nuclear transfer with fibroblasts bearing loss of heterozygosity mutations. Proc Natl Acad Sci USA 2004; 101:7335–7340.PubMedCrossRefGoogle Scholar
  76. 76.
    Gaudet F, Rideout WM, Meissner A et al. Dnmtl expression in pre-and postimplantation em-bryogenesis and the maintenance of LAP silencing. Molecular and Cellular Biology 2004; 24(4):1640–1648.PubMedCrossRefGoogle Scholar
  77. 77.
    Wolff GL, Kodell RL, Moore SR et al. Maternal epigenetics and methyl supplements affect agouti gene expression in a(Vy)/a mice. FASEB Journal 1998; 12(11):949–957.PubMedGoogle Scholar
  78. 78.
    Jaenisch R, Bird A. Epigenetic regulation of gene expression: How the genome integrates intrinsic and environmental signals [Review]. Nat Genet 2003; 33(Suppl S):245–254.PubMedCrossRefGoogle Scholar
  79. 79.
    Pray LA. Epigenetics: Genome, meet your environment. Scientist 2004; 18(13):14.Google Scholar
  80. 80.
    Santos F, Hendrich B, Reik W et al. Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev Biol 2002; 241(1):172–182.PubMedCrossRefGoogle Scholar
  81. 81.
    Bourc’his D, Le Bourhis D, Patin D et al. Delayed and incomplete reprogramming of chromosome methylation patterns in bovine cloned embryos. Current Biology 2001; 11(19):1542–1546.CrossRefGoogle Scholar
  82. 82.
    Dean W, Santos F, Stojkovic M et al. Conservation of methylation reprogramming in mammalian development: Aberrant reprogramming in cloned embryos. Proc Natl Acad Sci USA 2001; 98(24):13734–13738.PubMedCrossRefGoogle Scholar
  83. 83.
    Humpherys D, Eggan K, Akutsu H et al. Epigenetic instability in ES cells and cloned mice. Science 2001; 293(5527):95–97.PubMedCrossRefGoogle Scholar
  84. 84.
    Rideout WM, Eggan K, Jaenisch R. Nuclear cloning and epigenetic reprogramming of the genome. Science 2001; 293(5532):1093–1098.PubMedCrossRefGoogle Scholar
  85. 85.
    Klassen HJ, Warfving K, Kiilgaard JF et al. Transplantation of retinal progenitor cells from GFP-transgenic pigs to the injured retina of allogeneic recipients. Investigative Ophthalmology and Visual Science 2004; 45(5400 Suppl 2):U646.Google Scholar
  86. 86.
    Shatos MA, Klassen HJ, Schwartz PH et al. Isolation of projenitor cells from retina and brain of the GFP-transgenic pig. Investigative Ophthalmology and Visual Science 2004; 45(5406 Suppl 2):U647.Google Scholar
  87. 87.
    Webster NL, Forni M, Bacci ML et al. Multi-transgenic pigs expressing three fluorescent proteins produced with high efficiency by sperm mediated gene transfer. Mol Reprod Dev 2005; 72:68–72.PubMedCrossRefGoogle Scholar
  88. 88.
    Beschorner W, Joshi SS, Prather R et al. Selective and conditional depletion of pig cells with transgenic pigs and specific liposomes. Xenotransplantation 2003; 10(5):497.Google Scholar
  89. 89.
    Beschorner W, Prather R, Sosa C et al. Transgenic pigs expressing the suicide gene thymidine kinase in the liver. Xenotransplantation 2003; 10(5):530.Google Scholar
  90. 90.
    Lai LX, Kolber-Simonds D, Park KW et al. Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 2002; 295(5557):1089–1092.PubMedCrossRefGoogle Scholar
  91. 91.
    Kuwaki K, Tseng YL, Dor F et al. Heart transplantation in baboons using 1,3-galactosyl trans-ferase gene-knockout pigs as donors: Initial experience. Nature Medicine 2005; 11(1):29–31.PubMedCrossRefGoogle Scholar
  92. 92.
    Yamada K, Yazawa K, Shimizu A et al. Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha 1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue. Nature Medicine 2005; 11(1):32–34.PubMedCrossRefGoogle Scholar
  93. 93.
    Henderson KK, Turk JR, Rush JWE et al. Endothelial function in coronary arterioles from pigs with early-stage coronary disease induced by high-fat, high-cholesterol diet: Effect of exercise. Journal of Applied Physiology 2004; 97(3):1159–1168.PubMedCrossRefGoogle Scholar
  94. 94.
    Dobrinski I, Avarbock MR, Brinster RL. Germ cell transplantation from large domestic animals into mouse testes. Mol Reprod Dev 2000; 57(3):270–279.PubMedCrossRefGoogle Scholar
  95. 95.
    Poggiali P, Scoarughi GL, Lavitrano M et al. Construction of a swine artificial chromosome: A novel vector for transgenesis in the pig. Biochimie 2002; 84(11):1143–1150.PubMedCrossRefGoogle Scholar
  96. 96.
    Collas P. Nuclear reprogramming in cell-free extracts. Philosophical Transactions of the Royal Society of London-Series B: Biological Sciences 2003; 358(1436):1389–1395.PubMedCrossRefGoogle Scholar
  97. 97.
    Schneider-Schaulies J, Martin MJ, Logan JS et al. CD46 transgene expression in pig peripheral blood mononudear cells does not alter their susceptibility to measles virus or their capacity to downregulate endogenous and transgenic CD46. Journal of General Virology 2000; 81 (Part 6):1431–1438.PubMedGoogle Scholar
  98. 98.
    Diamond LE, Quinn CM, Martin MJ et al. A human CD46 transgenic pig model system for the study of discordant xenotransplantation. Transplantation 2001; 71(1):132–142.PubMedCrossRefGoogle Scholar
  99. 99.
    Langford GA, Yannoutsos N, Cozzi E et al. Production of pigs transgenic for human decay accelerating factor. Transplant Proc 1994; 26(3):1400–1401.PubMedGoogle Scholar
  100. 100.
    Fodor WL, Williams BL, Matis LA et al. Expression of a functional human complement inhibitor in a transgenic pig as a model for the prevention of xenogeneic hyperacute organ rejection. Proc Natl Acad Sci USA 1994; 91(23):11153–11157.PubMedCrossRefGoogle Scholar
  101. 101.
    Miyagawa S, Murakami H, Murase A et al. Transgenic pigs with human N-acetylglucosaminyl-transferase III. Transplant Proc 2001; 33(1–2):742–743.PubMedCrossRefGoogle Scholar
  102. 102.
    Phelps CJ, Koike C, Vaught TD et al. Production of alpha 1,3-galactosyltransferase-deficient pigs. Science 2003; 299(5605):411–414.PubMedCrossRefGoogle Scholar
  103. 103.
    Koike C, Kannagi R, Takuma Y et al. Introduction of Alpha(1,2)-fucosyltransferase and its effect on alpha-gal epitopes in transgenic pig. Xenotransplantation 1996; 3(1 Part 2):81–86.CrossRefGoogle Scholar
  104. 104.
    Tu CF, Tsuji K, Lee KH et al. Generation of HLA-DP transgenic pigs for the study of xenotransplantation. Inter Surg 1999; 84(2):176–182.Google Scholar
  105. 105.
    Tu CF, Hsieh SL, Lee JM et al. Successful generation of transgenic pigs for human decay-accelerating factor and human leucocyte antigen DQ. Transplant Proc 2000; 32(5):913–915.PubMedCrossRefGoogle Scholar
  106. 106.
    Lee JM, Tu CF, Yang PW et al. Reduction of human-to-pig cellular response by alteration of porcine MHC with human HLA DPW0401 exogenes. Transplantation 2002; 73(2):193–197.PubMedCrossRefGoogle Scholar
  107. 107.
    Lai LX, Park KW, Cheong HT et al. Transgenic pig expressing the enhanced green fluorescent protein produced by nuclear transfer using colchicine-treated fibroblasts as donor cells. Mol Reprod Dev 2002; 62(3):300–306.PubMedCrossRefGoogle Scholar
  108. 108.
    Webster NL, Forni M, Bacci ML et al. Multi-transgenic pigs expressing three fluorescent proteins produced with high efficiency by sperm mediated gene transfer. Mol Reprod Dev 2005; 72(1):68–76.PubMedCrossRefGoogle Scholar
  109. 109.
    Hao Y, Yong HY, Murphy CN et al. Production of transgenic cloned piglets by using porcine fetal fibroblasts overexpressing endothelial nitric oxide synthase (eNOS). Reprod Fert Dev 2006; 18:109w.CrossRefGoogle Scholar
  110. 110.
    Prather RS et al. Work in progress.Google Scholar
  111. 111.
    Sharma A, Martin MJ, Okabe JF et al. An isologous porcine promoter permits high level expression of human hemoglobin in transgenic swine. Bio-Technology 1994; 12(1):55–59.PubMedGoogle Scholar
  112. 112.
    Lee TK, Bangalore N, Velander W et al. Activation of recombinant human protein C. Thrombosis Research 1996; 82(3):225–234.PubMedCrossRefGoogle Scholar
  113. 113.
    Paleyanda RK, Velander WH, Lee TK et al. Transgenic pigs produce functional human factor Viii in milk. Nat Biotechnol 1997; 15(10):971–975.PubMedCrossRefGoogle Scholar
  114. 114.
    Lindsay M, Gil GC, Cadiz A et al. Purification of recombinant DNA-derived factor DC produced in transgenic pig milk and fractionation of active and inactive subpopulations. J Chromatogr 2004A; 1026(1–2):149–157.CrossRefGoogle Scholar
  115. 115.
    Petters RM, Alexander CA, Wells KD et al. Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa. Nat Biotechnol 1997; 15(10):965–970.PubMedCrossRefGoogle Scholar
  116. 116.
    Chen MY, Tu CF, Huang SY et al. Augmentation of thermotolerance in primary skin fibroblasts from a transgenic pig overexpressing the porcine HSP70.2. AJAS (Asian-Australasian Journal of Animal Sciences) 2005; 18(1):107–112.Google Scholar
  117. 117.
    Pursel VG, Wall RJ, Solomon MB et al. Transfer of an ovine metallothionein-ovine growth hormone fusion gene into swine. J Anim Sci 1997; 75(8):2208–2214.PubMedGoogle Scholar
  118. 118.
    Nottle MB, Nagashima H, Verma PJ et al. Production and analysis of transgenic pigs containing a metallothionein porcine growth hormone gene construct. In: Murray JD, Anderson GB, Oberbauer AM et al, eds. Transgenic Animals in Agriculture. Wallingford, Oxon, England: CAB International, 1999:145–156, (ISBN 0-85199-85293-85195).Google Scholar
  119. 119.
    Hirabayashi M, Takahashi R, Ito K et al. A comparative study on the integration of exogenous DNA into mouse, rat, rabbit, and pig genomes. Exp Anim 2001; 50(2):125–131.PubMedCrossRefGoogle Scholar
  120. 120.
    Cifone D, Dominici FP, Pursel VG et al. Inability of heterologous growth hormone (GH) to regulate GH binding protein in GH-transgenic swine. J Anim Sci 2002; 80(7):1962–1969.PubMedGoogle Scholar
  121. 121.
    Pursel VG, Wall RJ, Mitchell AD et al. Expression of insulin-like growth factor-I in skeletal muscle of transgenic swine. In: Murray JD, Anderson GB, Oberbauer AM et al, eds. Transgenic Animals in Agriculture. 198 Madison Ave, New York, NY: CAB International, 1999:131–144, (10016-4341 USA).Google Scholar
  122. 122.
    Bleck GT. Production of bovine alpha-lactalbumin in the milk of transgenic pigs. J Anim Sci 1998; 76(12):3072–3078.PubMedGoogle Scholar
  123. 123.
    Golovan SP. Pigs expressing salivary phytase produce low-phosphorus manure. Nature Biotechnology 2001; 19(8):741–745, [erratum appears in Nat Biotechnol 2001 Oct;19 (10):979].PubMedCrossRefGoogle Scholar
  124. 124.
    Uchida M, Shimatsu Y, Onoe K et al. Production of transgenic miniature pigs by pronuclear microinjection. Transgenic Res 2001; 10(6):577–582.PubMedCrossRefGoogle Scholar
  125. 125.
    Saeki K, Matsumoto K, Kinoshita M et al. Functional expression of a Delta 12 fatty acid desaturase gene from spinach in transgenic pigs. Proc Natl Acad Sci USA 2004; 101(17):6361–6366.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Randall S. Prather
    • 1
  1. 1.Division of Animal Science, Food for the 21st Century, College of Food, Agriculture & Natural ResourcesUniversity of Missouri-ColumbiaColumbiaUSA

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