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Transgenic Farm Animals: Current Status and Perspectives for Agriculture and Biomedicine

  • Heiner Niemann
  • Wilfried Kues
  • Joseph W. Carnwath
Chapter
Part of the Ethics of Science and Technology Assessment book series (ETHICSSCI, volume 34)

Summary

The first transgenic livestock were produced in 1985 by microinjection of foreign DNA into zygotic pronuclei. This was the method of choice for more than 20 years, but more efficient protocols are now available, based on somatic cell nuclear transfer (SCNT) which permits targeted genetic modifications. Although the efficiency of transgenic animal production by microinjection technology is low, many animals with agriculturally important transgenic traits were produced. Typical applications included improved carcass composition, lactational performance, and wool production as well as enhanced disease resistance and reduced environmental impact. Transgenic animal production for biomedical applications has found broad acceptance. In 2006 the European Medicines Agency (EMEA) approved the commercialization of the first recombinant protein drug produced by transgenic animals. Recombinant antithrombin III, produced in the mammary gland of transgenic goats, was launched as ATryn® for prophylactic treatment of patients with congenital antithrombin deficiency. Pigs expressing human immunomodulatory genes have contributed to significant progress in xenotransplantation research with survival periods of non-human primates receiving transgenic porcine hearts or kidneys approaching six months. Lentiviral vectors and small interfering ribonucleic acid (siRNA) technology are also emerging as important tools for transgenesis. As the genome sequencing projects for various farm animal species progress, it has become increasingly practical to target the removal or modification of individual genes. We anticipate that this approach to animal breeding will be instrumental in meeting global challenges in agricultural production in the future and will open new horizons in biomedicine.

Keywords

Mammary Gland Transgenic Animal Human Artificial Chromosome Transgenic Goat Transgenic Sheep 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Anderson GB (1999) Embryonic stem cells in agricultural species. In: Murray JD, Anderson GB, Oberbauer AM, McGloughlin MM (eds) Transgenic Animals in Agriculture. CABI Publ., New York, USA, pp 57–66Google Scholar
  2. Archer GC, Dindot S, Friend TH, Walker S, Zaunbrecher G, Lawborn B, Piedrahita JA (2003) Hierarchical phenotype and epigenetic variation in cloned swine. Biol Reprod 69:430–436CrossRefGoogle Scholar
  3. Baguisi A, Behboodi E, Melican D, Pollock JS, Destrempes MM, Cammuso C, Williams JL, Nims SD, Porter CA, Midura P, Palacios MJ, Ayres SL, Denniston RS, Hayes ML, Ziomek CA, Meade HM, Godke RA, Gavin WG, Overström EW, Echelard Y (1999) Production of goats by somatic cell nuclear transfer. Nat Biotech 17(5):456–461CrossRefGoogle Scholar
  4. Baise E, Pire G, Leroy M, Gerardin J, Goris N, De Clercq K, Kerkhofs P, Desmecht D, (2004) Conditional expression of type I interferon-induced bovine Mx1 GTPase in a stable transgenic vero cell line interferes with replication of vesicular stomatitis virus. J Interferon & Cytokine Res 24(9):513–521Google Scholar
  5. Brambrink T, Wabnitz P, Halter R, Klocke R, Carnwath JW, Kues WA, Wrenzycki C, Paul D, Niemann H (2002) Application of cDNA arrays to monitor mRNA profiles in single preimplantation mouse embryos. Biotechniques 33(2):376–378Google Scholar
  6. Brophy B, Smolenski G, Wheeler T, Wells D, L’Huillier P, Laible G (2003) Cloned transgenic cattle produce milk with higher levels of b-casein and k-casein. Nat Biotechnol 21(2):157–162CrossRefGoogle Scholar
  7. Capecchi MR (1989) The new mouse genetics: Altering the genome by gene targeting. Trends Genet 5(3):70–76CrossRefGoogle Scholar
  8. Carter BD, Lai L, Park KW, Samuel M, Lattimer JC, Jordan K R, Estes DM, Besch- Williford C, Prather R (2002) Phenotyping of transgenic cloned pigs. Cloning Stem Cells 4:131–14CrossRefGoogle Scholar
  9. Castilla J, Pintado B, Sola I, Sáncez-Morgado JM, Enjuanes L (1998) Engineering passive immunity in transgenic mice secreting virus-neutralizing antibodies in milk. Nat Biotechnol 16(4):349–354CrossRefGoogle Scholar
  10. Chan AW, Homan EJ, Ballou LU, Burns JC, Bremel RD (1998) Transgenic cattle produced by reverse-transcribed gene transfer in oocytes. Proc Natl Acad Sci USA 95(24):14028–14033CrossRefGoogle Scholar
  11. Chang K, Qian J, Jiang M, Liu YH, Wu MC, Chen CD, Lai CK, Lo HL, Hsiao CT, Brown L, Bolen J Jr, Huang HI, Ho PY, Shih PY, Yao CW, Lin WJ, Chen CH, Wu FY, Lin YJ, Xu J, Wang K (2002) Effective generation of transgenic pigs and mice by linker based sperm-mediated gene transfer. BMC Biotechnol 2(1):5CrossRefGoogle Scholar
  12. Chavatte-Palmer P, Heyman Y, Richard C, Monget P, LeBourhis D, Kann G, Chilliard Y, Vignon X, Renard JP (2002) Clinical, hormonal, and hematologic characteristics of bovine calves derived from nuclei from somatic cells. Biol Reprod 66:1596–1603CrossRefGoogle Scholar
  13. Chou CY, Horng LS, Tsai HJ (2001) Uniform GFP-expression in transgenic medaka (Oryzias latipes) at the F0 generation. Transgenic Res 10:303–315CrossRefGoogle Scholar
  14. Cibelli JB, Stice SL, Golueke PL, Kane JJ, Jerry J, Blackwell C, Ponce de Leon FA, Robl JM (1998) Transgenic bovine chimeric offspring produced from somatic cell-derived stem like cells. Nat Biotech 16(7):642–646CrossRefGoogle Scholar
  15. Cibelli JB, Campbell KH, Seidel GE, West MD, Lanza RP (2002) The health profile of cloned animals. Nat Biotechnol 20:13–14CrossRefGoogle Scholar
  16. Clark J, Whitelaw B (2003) A future for transgenic livestock. Nat. Rev Genet 4(10):825–833CrossRefGoogle Scholar
  17. Clements JE, Wall RJ, Narayan O, Hauer D, Schoborg R, Sheffer D, Powell A, Carruth LM, Zink MC, Rexroad CE (1994) Development of transgenic sheep that express the Visna virus envelope gene. Virology 200(2):370–380CrossRefGoogle Scholar
  18. Copley MS, Berstan R, Dudd SN, Docherty G, Mukherjee AJ, Straker V, Payne S, Evershed RP (2003) Direct chemical evidence for widespread dairying in prehistoric Britain. Proc Natl Acad Sci USA 100(4):1524–1529CrossRefGoogle Scholar
  19. Corbel YC, Rossi F (2002) Latest developments and in vivo use of the Tet system: ex vivo and in vivo delivery of tetracycline-regulated genes. Curr Opin Biotechnol 13:448–452CrossRefGoogle Scholar
  20. Cozzi E, White DJG (1995) The generation of transgenic pigs as potential organ donors for humans. Nat Med 1:964–966CrossRefGoogle Scholar
  21. D’Agnillo F, Chang TM (1998) Polyhemoglobin-superoxide dismutase-catalase as a blood substitute with antioxidant properties. Nat Biotechnol 16(7):667–671CrossRefGoogle Scholar
  22. Dai Y, Vaught TD, Boone J, Chen SH, Phelps CJ, Ball S, Monahan JA, Jobst PM, McCreath KJ, Lamborn AE, Cowell-Lucero JL, Wells KD, Colman A, Polejaeva IA, Ayares DL (2002) Targeted disruption of the α1,3-galactosyltransferase gene in cloned pigs. Nat Biotechnol 20(3):251–255CrossRefGoogle Scholar
  23. Dallas A, Vlassow A (2006) RNAi: A novel antisense technology and its therapeutic potential. Med Sci Monit 12:RA67–RA74Google Scholar
  24. Damak S, Su H, Jay NP, Bullock DW (1996a) Improved wool production in transgenic sheep expressing insulin-like growth factor 1. Biotechnology 14(2):185–188CrossRefGoogle Scholar
  25. Damak S, Jay NP, Barrell GK, Bullock DW (1996b) Targeting gene expression to the wool follicle in transgenic sheep. Biotechnology 14(2):181–184CrossRefGoogle Scholar
  26. Denning C, Burl S, Ainslie A, Bracken J, Dinnyes A, Fletcher J, King T, Ritchie M, Ritchie WA, Rollo M, de Sousa P., Travers A, Wilmut I, Clark AJ (2001) Deletion of the α(1,3)galactosyltransferase (GGTA1) and the prion protein (PrP) gene in sheep. Nat Biotechnol 19(6):559–562CrossRefGoogle Scholar
  27. Deppenmeier S, Bock O, Mengel M, Niemann H, Kues W, Lemme E, Wirth D, Wonigeit K, Kreipe H (2006) Health status of transgenic pig lines expressing human complement regulator protein CD59. Xenotransplantation 13:345–356CrossRefGoogle Scholar
  28. Dieckhoff B, Karlas A, Hofmann A, Kues WA, Petersen B, Pfeifer A, Niemann H (2007) Inhibition of porcine endogenous retroviruses (PERV) in primary porcine cells by RNA interference using lentiviral vectors. Archives of Virology 152:629–34CrossRefGoogle Scholar
  29. Dieckhoff B, Petersen B, Kues WA, Kurth R, Niemann H, Denner J (2008) Knockdown of porcine endogenous retrovirus (PERV) expression by PERV-specific shRNA in transgenic pigs. Xenotransplantation 15:36–45CrossRefGoogle Scholar
  30. Downing GJ, Battey JF Jr (2004) Technical assessment of the first 20 years of research using mouse embryonic stem cell lines. Stem Cells 22(7):1168–1180CrossRefGoogle Scholar
  31. Dyck MK, Lacroix D, Pothier F, Sirard MA (2003) Making recombinant proteins in animals – different systems, different applications. Trends Biotechnol 21(9):394–399CrossRefGoogle Scholar
  32. Echelard Y, Ziome C, Meade H (2006) Production of recombinant therapeutic proteins in the milk of transgenic animals. BioPharm Intern 2(8):1–6 (http://www.biopharminternational.com/biopharm/content, July 2008)Google Scholar
  33. Enright BP, Taneja M, Schreiber D, Riesen J, Tian XC, Fortune JE, Yang X (2002) Reproductive characteristics of cloned heifers derived from adult somatic cells. Biol Reprod 66:291–296CrossRefGoogle Scholar
  34. Fändrich F, Lin X, Chai G., Schulze M, Ganten D, Bader M, Holle J, Huang DS, Parwaresch R, Zavazava N, Binas B (2002) Preimplantation-stage stem cells induce longterm allogeneic graft acceptance without supplementary host conditioning. Nat Med 8(2):171–178CrossRefGoogle Scholar
  35. Food and Drug Administration USA (2003) FDA statement regarding Glofish (http://www.fda.gov/bbs/topics/NEWS/2003/NEW00994.html, July 2007)
  36. Food and Drug Administration (2008) Animal cloning: a risk assessment – final.Google Scholar
  37. Rockville, MD: United States Food and Drug Administration (http://www.fda.gov/cvm/CloneRiskAssessment_Final.htm, July 2007)
  38. Furth PA, St Onge L, Boger H, Gruss P, Gossen M, Kistner A, Bujard H, Hennighausen L (1994) Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter. Proc Natl Acad Sci USA 91:9302–9306CrossRefGoogle Scholar
  39. Gjorret JO, Maddox-Hyttel P (2005) Attempts towards derivation and establishment of bovine embryonic stem cell-like cultures. Reprod Fert Dev 17:113–124CrossRefGoogle Scholar
  40. Golding MC, Long CR, Carmell MA, Hannon GJ, Westhusin ME (2006) Suppression of prion protein in livestock by RNA interference. Proc Natl Acad Sci USA 103:5285–5290CrossRefGoogle Scholar
  41. Golovan SP, Meidinger RG, Ajakaiye A, Cottrill M, Wiederkehr MZ, Barney DJ, Plante C, Pollard JW, Fan MZ, Hayes MA, Laursen J, Hjorth JP, Hacker RR, Phillips JP, Forsberg CW (2001) Pigs expressing salivary phytase produce lowphosphorus manure. Nat Biotechnol 19(8):741–745CrossRefGoogle Scholar
  42. Gong W, Wan H, Tay TL, Wang H, Chen M, Yan T (2003) Development of transgenic fish for ornamental and bioreactor by strong expression of fluorescent proteins in the skeletal muscle. Biochemical and Biophysical Research Communications 308:58–63CrossRefGoogle Scholar
  43. Govoni K, Tian XC, Kazmer GW, Taneja M, Enright BP, Rivard AL, Yang X, Zinn SA (2002) Age-related changes of the somatotropic axis in cloned Holstein calves. Biol Reprod 66:1293–1298CrossRefGoogle Scholar
  44. Grosse-Hovest L, Muller S, Minoia R, Wolf E, Zakhartchenko V, Wenigerkind H, Lassnig C, Besenfelder U, Müller M, Lytton SD, Jung G, Brem G (2004) Cloned transgenic farm animals produce a bispecific antibody for T cell-mediated tumor cell killing. Proc Natl Acad Sci USA. 101(18):6858–6863CrossRefGoogle Scholar
  45. Grunwald KA, Schueler K, Uelmen PJ, Lipton BA, Kaiser M, Buhman K, Attie AD (1999) Identification of a novel Arg->Cys mutation in the LDL receptor that contributes to spontaneous hypercholesterolemia in pigs. J Lipid Res 40(3):475–485Google Scholar
  46. Hammer RE, Pursel VG, Rexroad CE Jr, Wall RJ, Bolt DJ, Ebert KM, Palmiter RD, Brinster RL (1985) Production of transgenic rabbits, sheep and pigs by microinjection. Nature 315(6021):680–683CrossRefGoogle Scholar
  47. Hansen K, Khanna C (2004) Spontaneous and genetically engineered animal models; use in preclinical cancer drug development. Eur J Cancer 40(6):858–880CrossRefGoogle Scholar
  48. Haskell RE, Bowen R (1995) Efficient production of transgenic cattle by retroviral infection of early embryos. Mol Reprod Dev 40(3):386–390CrossRefGoogle Scholar
  49. Hofmann A, Kessler B, Ewerling S, Weppert M, Vogg B, Ludwig H, Stojkovic M, Boelhauve M, Brem G, Wolf E, Pfeifer A (2003) Efficient transgenesis in farm animals by lentiviral vectors. EMBO Rep 4(11):1054–1060CrossRefGoogle Scholar
  50. Hofmann A, Zakhartchenko V, Weppert M, Sebald H, Wenigerkind H, Brem G, Wolf E, Pfeifer A (2004) Generation of transgenic cattle by lentiviral gene transfer into oocytes. Biol Reprod 71(2):405–409CrossRefGoogle Scholar
  51. Hofmann A, Kessler B, Ewerling S, Kabermann A, Brem G, Wolf E, Pfeifer A (2006) Epigenetic regulation of lentiviral transgene vectors in a large animal model. Mol Ther 13:59–66CrossRefGoogle Scholar
  52. Honaramooz A, Behboodi E, Megee SO, Overton SA, Galantino-Homer H, Echelard Y, Dobrinski I (2003) Fertility and germline transmission of donor haplotype following germ cell transplantation in immunocompetent goats. Biol Reprod 69:1260–1264CrossRefGoogle Scholar
  53. Honaramooz A, Megee S, Zeng W, Destrempes MM, Overton SA, Luo J, Galantino- Homer H, Modelski M, Chen F, Blash, S, Melican DT, Gavin WG, Ayres S, Yang F, Wang PJ, Echelard Y, Dobrinski I (2007) Adeno-associated virus (AAV)- mediated transduction of male germ line stem cells results in transgene transmission after germ cell transplantation. FASEB Journal fj.07-8935Google Scholar
  54. Hornen N, Kues WA, Carnwath JW, Lucas-Hahn A, Petersen B, Hassel B, Niemann H (2007) Production of viable pigs from fetal somatic stem cells. Cloning Stem Cells 9:364–373CrossRefGoogle Scholar
  55. Huang YJ, Huang Y, Baldassarre H, Wang B, Lazaris A, Leduc M, Bilodeau AS, Bellemare A, Cote M, Herskovits P, Touati M, Turcotte C, Valeanu L, Lemee N, Wilgus H, Begin I, Bhatia B, Rao K, Neveu N, Brochu E, Pierson J, Hockley DC, Cerasoli DM, Lenz DE, Karatzas CN, Langermann S (2007) Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning. Proc Natl Acad Sci USA 104 (34):13603–13608CrossRefGoogle Scholar
  56. Hughes TR, Roberts CJ, Dai H, Jones AR, Meyer MR, Slade D, Burchard J, Dow S, Ward TR, Kidd MJ, Friend SH, Marton MJ (2000) Widespread aneuploidy revealed by DNA microarray expression profiling. Nat Genet 25(3):333–337CrossRefGoogle Scholar
  57. Humpherys D, Eggan K, Akutsu H, Hochedlinger K, Rideout WM 3rd, Biniszkiewicz D, Yanagimachi R, Jaenisch R (2001) Epigenetic instability in ES cells and cloned mice. Science 293:95–97CrossRefGoogle Scholar
  58. Hyttinen JM, Peura T, Tolvanen M, Aalto J, Alhonen L, Sinervirta R, Halmekyto M, Myohanen S, Janne J (1994) Generation of transgenic dairy cattle from transgene-analyzed and sexed embryos produced in vitro. Biotechnology 12(6):606–608CrossRefGoogle Scholar
  59. Ibrahim Z, Busch J, Awwad M, Wagner R, Wells K, Cooper DKC (2006) Selected physiologic compatibilities and incompatibilities between human and porcine organ systems. Xenotransplantation 13:488–499CrossRefGoogle Scholar
  60. Iqbal K, Kues WA, Niemann H (2007) Parent-of-origin dependent gene-specific knock down in mouse embryos. Biochemical and Biophysical Research Communications 358:727–32CrossRefGoogle Scholar
  61. Irgang M, Sauer IM, Karlas A, Zeilinger K, Gerlach J, Kurth R, Neuhaus P, Denner J (2003) Porcine endogenous retroviruses: no infection in patients treated with a bioreactor based on porcine liver cells. J Clin Virology 28:141–154CrossRefGoogle Scholar
  62. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418(6893):41–49CrossRefGoogle Scholar
  63. Jost B, Vilotte JL, Duluc I, Rodeau JL, Freund JN (1999) Production of low-lactose milk by ectopic expression of intestinal lactase in the mouse mammary gland. Nat Biotechnol 17(2):160–164CrossRefGoogle Scholar
  64. Karatzas CN, Turner JD (1997) Toward altering milk composition by genetic manipulation: current status and challenges. J Dairy Sci 80(9):2225–2232Google Scholar
  65. Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, Shaffer J, Preffer FI, Ding R, Sharma V, Fishman JA, Dey B, Ko DSC, Hertl M, Goes NB, Wong W, Williams WW Jr, Colvin RB, Sykes M, Sachs DH (2008) HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression. NEJM 358(4):353–361CrossRefGoogle Scholar
  66. Kilby NJ, Snaith MR, Murray JAH (1993) Site-specific recombinases: tools for genome engineering. Trends Genet 9(12):413–421CrossRefGoogle Scholar
  67. Krimpenfort P, Rademakers A, Eyestone W, van der Schans A, van den Broek S, Kooiman P, Kootwijk E, Platenburg G, Pieper F, Strijker R, de Boer H (1991) Generation of transgenic dairy cattle using in vitro embryo production. Biotechnology 9(9):844–847CrossRefGoogle Scholar
  68. Kubota C, Tian XC, Yang X (2004) Serial bull cloning by somatic cell nuclear transfer. Nature Biotechnology 22:693–694CrossRefGoogle Scholar
  69. Kues WA, Niemann H (2004) The contribution of farm animals to human health. Trends Biotechnol 22(6):286–294CrossRefGoogle Scholar
  70. Kues WA, Carnwath JW, Niemann H (2005a) From fibroblasts to stem cells: implications for cell therapies and somatic cloning. Reprod Fertil Dev 17(1,2):125–134CrossRefGoogle Scholar
  71. Kues WA, Petersen B, Mysegades W, Carnwath JW, Niemann H (2005b) Isolation of murine and porcine fetal stem cells from somatic tissue. Biol Reprod 72(4):1020–1028CrossRefGoogle Scholar
  72. Kues WA, Schwinzer R, Wirth D, Verhoeyen E, Lemme E, Herrmann D, Barg- Kues B, Hauser H, Wonigeit H, Niemann H (2006) Epigenetic silencing and tissue independent expression of a novel tetracycline inducible system in doubletransgenic pigs. FASEB Journal Express doi: 10.1096/fj.05-5415fje; printed short version: FASEB J 20:1200–1202Google Scholar
  73. Kumugai S (2002) Safety of animal foods that utilize cloning technology. Report to the Japanese Ministry for Agriculture, Forestry and Fishery (MAFF)Google Scholar
  74. Kuroiwa Y, Kasinathan P, Choi YJ, Naeem R, Tomizuka K, Sullivan EJ, Knott JG, Duteau A, Goldsby RA, Osborne BA, Ishida I, Robl JM (2002) Cloned transchromosomic calves producing human immunoglobulin. Nat Biotechnol 20(9):889–894CrossRefGoogle Scholar
  75. Kuwaki K, Tseng YL, Dor FJ, Shimizu A, House SL, Sanderson TM, Lanceros CJ, Rabharasuth DD, Cheng J, Moran K, Hisashi Y, Mueller N, Yamadoa K, Greenstein JL, Hawley RJ, Patience C, Awwad M, Fishman JA, Robson SC, Schuurman HJ, Sachs DH, Cooper DK. (2005) Heart transplantation in baboons usion a1,3- glactosyltransferase knock out pigs as donors: initial experiments. Nat Med 11:29–31CrossRefGoogle Scholar
  76. Lai L, Kang JX, Li R, Wang J, Witt WT, Yong HY, Hao Y, Wax DM, Murphy CN, Rieke A, Samuel M, Linville ML, Korte SW, Evans RW, Starzl TE, Prather RS, Dai Y (2006) Generation of cloned transgenic pigs rich in omega-3 fatty acids. Nat Biotechnol 24(4):435–436CrossRefGoogle Scholar
  77. Lai L, Kolber-Simonds D, Park KW, Cheong HT, Greenstein JL, Im GS, Samuel M, Bonk A, Rieke A, Day BN, Murphy CN, Carter DB, Hawley RJ, Prather RS (2002) Production of α1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 295(5557):1089–1092CrossRefGoogle Scholar
  78. Lanza RP, Cibelli JB, Faber D, Sweeney RW, Henderson B, Nevala W, West MD, Wettstein PJ (2001) Cloned cattle can be healthy and normal. Science 294:1893–1894CrossRefGoogle Scholar
  79. Lavitrano M, Camaioni A, Fazio VM, Dolci S, Farace MG, Spadafora C (1989) Sperm cells as vectors for introducing foreign DNA into eggs: genetic transformation of mice. Cell 57(5):717–723CrossRefGoogle Scholar
  80. Lavitrano M, Bacci ML, Forni M, Lazzereschi D, Di Stefano C, Fioretti D, Giancotti P, Marfe G, Pucci L, Renzi L, Wang H, Stoppacciaro A, Stassi G, Sargiacomo M, Sinibaldi P, Turchi V, Giovannoni R, Della Casa G, Seren E, Rossi G (2002) Efficient production by sperm-mediated gene transfer of human decay accelerating factor (hDAF) transgenic pigs for xenotransplantation. Proc Nat Acad Sci USA 99(22):14230–14235CrossRefGoogle Scholar
  81. Lee F, Mulligan R, Berg P, Ringold G (1981) Glucocorticoids regulate expression of dihydrofolate reductase cDNA in mouse mammary tumour virus chimaeric plasmids. Nature 294:228–232CrossRefGoogle Scholar
  82. Lewandowski M (2001) Conditional control of gene expression in the mouse. Nature Reviews 2:743–755CrossRefGoogle Scholar
  83. Li Z, Engelhardt JF (2003) Progress toward generating a ferret model of cystic fibrosis by somatic cell nuclear transfer. Reprod Biol Endocrinol 1(1):83CrossRefGoogle Scholar
  84. Lo D, Pursel V, Linton PJ, Sandgren E, Behringer R, Rexroad C, Palmiter RD, Brinster RL (1991) Expression of mouse IgA transgenic mice, pigs and sheep. Eur J Immunol 21(4):1001–1006CrossRefGoogle Scholar
  85. Ma JK, Drake PM, Christou P (2003) The production of recombinant pharmaceutical proteins in plants. Nat Rev Genet 4(10):794–805CrossRefGoogle Scholar
  86. Maga EA, Anderson GB, Murray JD (1995) The effects of mammary gland expression of human lysozyme on the properties of milk from transgenic mice. J Dairy Sci 78(12):2645–2652Google Scholar
  87. Maga EA, Murray JD (1995) Mammary gland expression of transgenes and the potential for altering the properties of milk. Biotechnology 13(13):1452–1457Google Scholar
  88. Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, Stadtfeld M, Yacheko RJ, Janenisch R, Hochedlinger K (2007) Directly reprogrammed fibroblasts show epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1:55–70CrossRefGoogle Scholar
  89. Mahmoud TH, McCuen BW, Hao Y, Moon SJ, Tatebayashi M, Stinnett S, Petters RM, Wong F (2003) Lensectomy and vitrectomy decrease the rate of photoreceptor loss in rhodopsin P347L transgenic pigs. Graefes Arch Clin Exp Ophtalmol 241(4):298–308CrossRefGoogle Scholar
  90. Massoud M, Attal J, Thepot D, Pointu H, Stinnakre MG, Theron MC, Lopez C, Houdebine LM (1996) The deleterious effects of human erythropoietin gene driven by the rabbit whey acidic protein gene promoter in transgenic rabbits. Reprod Nutr Dev 36(5):555–563CrossRefGoogle Scholar
  91. Mayo KE, Warren R, Palmiter RD (1982) The mouse metallothionein-I gene is transcriptionally regulated by cadmium following transfection into human or mouse cells. Cell 29:99–108CrossRefGoogle Scholar
  92. Meade HM, Echelard Y, Ziomek CA, Young JM, Harvery M, Cole ES, Groet S, Curling JM (1999) Expression of recombinant proteins in the milk of transgenic animals. In: Fernandez JM, Hoeffler JP (eds) Gene Expression Systems, Academic Press San Diego, USA, pp 399–427CrossRefGoogle Scholar
  93. Miller HI (2007) Food from cloned animals is part of our brave old world. Trends Biotechnol 25:201–203CrossRefGoogle Scholar
  94. Miller KF, Bolt DJ, Pursel VG, Hammer RE, Pinkert CA, Palmiter RD, Brinster RL (1989) Expression of human or bovine growth hormone gene with a mouse metallothionein-1 promoter in transgenic swine alters the secretion of porcine growth hormone and insulin-like growth factor-I. J Endocrinol 120:481–488CrossRefGoogle Scholar
  95. Müller M, Brem G (1991) Disease resistance in farm animals. Experientia 47(9):923–934CrossRefGoogle Scholar
  96. Müller M, Brenig B, Winnacker EL, Brem G (1992) Transgenic pigs carrying cDNA copies encoding the murine Mx1 protein which confers resistance to influenza virus infection. Gene 121(2):263–270CrossRefGoogle Scholar
  97. National Academy of Sciences of the USA (2002) Safety of genetically engineered foods: Approaches to assessing unintended health effects. Sub-report on methods and mechanisms of genetic manipulation and cloning of animals. The National Academic Press. Washingthon DC, 217–235Google Scholar
  98. Niemann H (2004) Transgenic pigs expressing plant genes. Proc Natl Acad Sci USA 101(19):7211–7212CrossRefGoogle Scholar
  99. Niemann H, Halter R, Carnwath JW, Herrmann D, Lemme E, Paul D (1999) Expression of human blood clotting factor VIII in the mammary gland of transgenic sheep. Transgenic Res 8:237–247CrossRefGoogle Scholar
  100. Niemann H, Kues WA (2003) Application of transgenesis in livestock for agriculture and biomedicine. Anim Reprod Sci 79:291–317CrossRefGoogle Scholar
  101. Niemann H, Kues W, Carnwath JW (2005) Transgenic farm animals: present and future. Rev sci tech Off int Epiz 24(1):285–298Google Scholar
  102. Niemann H, Kues, WA (2007) Transgenic farm animals: an update. Reproduction, Fertility and Development 19:762–770CrossRefGoogle Scholar
  103. Niemann H, Carnwath JW, Kues WA (2007) Application of DNA array technology to mammalian embryos. Theriogenology 68 (Suppl 1):165–177CrossRefGoogle Scholar
  104. Nottle MB, Nagashima H, Verma PJ, Du ZT, Grupen CG, Mellfatrick SM, Ashman RJ, Harding MP, Giannakis C, Wigley PL, Lyons IG, Harrison DT, Luxford BG, Campbell RG, Crawford RJ, Robins AJ (1999) Production and analysis of transgenic pigs containing a metallothionein porcine growth hormone gene construct. In: Murray JD, Oberbauer AM, McGloughlin MM (eds) Transgenic Animals in Agriculture CABI Publ, New York USA, pp 145–156Google Scholar
  105. Ogonuki N, Inoue K, Yamamoto Y, Noguchi Y, Tanemur, K, Suzuki O, Nakayama H, Doi K, Ohtomo Y, Satoh M, Nishida A, Ogura A (2002) Early death of mice cloned from somatic cells. Nat Genet 30:253–254CrossRefGoogle Scholar
  106. Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448:260–262CrossRefGoogle Scholar
  107. Pace MM, Augenstein ML, Betthauser JM, Childs LA, Eilertsen KJ, Enos JM, Forsberg EJ, Golueke PJ, Graber DF, Kemper JC, Koppang RW, Lange G, Lesmeister TL, Mallon KS, Mell GD, Misica PM, Pfister-Genskow M, Strelchenko NS, Voelker GR, Watt SR, Bishop MD (2002) Ontogeny of cloned cattle to lactation. Biol Reprod 67:334–339CrossRefGoogle Scholar
  108. Palmarini M, Fan H (2001) Retrovirus-induced ovine pulmonary adenocarcinoma, an animal model for lung cancer. J Natl Cancer Inst 93(21):1603–1614CrossRefGoogle Scholar
  109. Panarace M, Agüero JI, Garrote M, Jauregui G, Segovia A, Cané L (2007) How healthy are clones and their progeny: 5 years of field experience. Theriogenology 67:142–151CrossRefGoogle Scholar
  110. Perry ACF, Wakayama T, Kishikawa H, Kasai T, Okabe M, Toyoda Y, Yanagimachi R (1999) Mammalian transgenesis by intracytoplasmic sperm injection. Science 284(5417):1180–1183CrossRefGoogle Scholar
  111. Perry AC, Rothman A, de las Heras JI, Feinstein P, Mombaerts P, Cooke HJ, Wakayama T (2001) Efficient metaphase II transgenesis with different transgene archetypes. Nat Biotechnol 19(11):1071–1073CrossRefGoogle Scholar
  112. Petersen B, Lucas-Hahn A, Lemme E, Hornen N, Hassel P, Niemann H (2007) Preovulatory embryo transfer increases cloning efficiencies in pigs. Reprod Fertil Dev 19:155 (abstract)CrossRefGoogle Scholar
  113. Petersen B, Lucas-Hahn A, Herrmann D, Kues WA, Ramackers W, Bergmann S, Carnwath JW, Winkler M, Niemann H (2008) Production of pigs transgenic for human hemeoxygenase-I by somatic nuclear transfer. ReprodFertil Dev 20:234 (abstract)Google Scholar
  114. Petters RM, Alexander CA, Wells KD, Collins EB, Sommer JR, Blanton MR, Rojas G, Hao Y, Flowers WL, Banin E, Cideciyan AV, Jacobson SG, Wong F (1997) Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa. Nat Biotechnol 15(10):965–970CrossRefGoogle Scholar
  115. Phelps CJ, Koike C, Vaught TD, Boone J, Wells KD, Chen SH, Ball S, Specht SM, Polejaeva IA, Monahan JA, Jobst PM, Sharma SB, Lamborn AE, Garst AS, Moore M, Demetris AJ, Rudert WA, Bottino R, Bertera S, Trucco M, Starzl TE, Dai Y, Ayares DL (2003) Production of α 1,3-galactosyltransferasedeficient pigs. Science 299:411–414CrossRefGoogle Scholar
  116. Plasterk RH (2002) RNA silencing: the genomes immune system. Science 296:1263–1265CrossRefGoogle Scholar
  117. Platenburg GJ, Kootwijk EAP, Kooiman PM, Woloshuk SL, Nuijens JH, Krimpenfort PJA, Pieper FR, de Boer HA, Strijker R (1994) Expression of human lactoferrin in milk of transgenic mice. Transgenic Res 3(2):99–108CrossRefGoogle Scholar
  118. Platt JL, Lin SS (1998) The future promises of xenotransplantation. Ann NY Acad Sci 862:5–18CrossRefGoogle Scholar
  119. Pursel VG, Pinkert CA, Miller KF, Bolt DJ, Campbell RG, Palmiter RD, Brinster RL, Hammer RE (1989) Genetic engineering of livestock. Science 244(4910):1281–1288CrossRefGoogle Scholar
  120. Pursel VG, Wall RJ, Mitchell AD, Elsasser TH, Solomon MB, Coleman ME, Mayo F, Schwartz RJ (1999) Expression of insulin-like growth factor-I in skeletal muscle of transgenic pigs. In: Murray JD, Oberbauer AM, McGloughlin MM (eds) Transgenic Animals in Agriculture. CABI Publ, New York, USA, pp 131–144Google Scholar
  121. Rapacz J, Hasler-Rapacz J (1989) Animal models: the pig. In: Sparkes RS, Lusis AJ (eds) Genetic Factors in Atherosclerosis: model systems. Karger, Basel, Switzerland, pp 139–169Google Scholar
  122. Reh WA, Maga EA, Collette NM, Moyer A, Conrad-Brink JS, Taylor SJ (2004) Hot topic: using a stearoyl-CoA desaturase transgene to alter milk fatty acid composition. Journal of Dairy Science 87:3510–3514CrossRefGoogle Scholar
  123. Renard JP, Chastant S, Chesne P, Richard C, Marchal J, Cordonnier N, Chavatte P, Vignon X (1999) Lymphoid hypoplasia and somatic cloning. Lancet 353:1489–1491CrossRefGoogle Scholar
  124. Rhind SM, King TJ, Harkness LM, Bellamy C, Wallace W, DeSousa P, Wilmut, I (2003) Cloned lambs–lessons from pathology. Nat Biotechnol 21:744–745CrossRefGoogle Scholar
  125. Richt JA, Kasinathan P, Hamir AN, Castilla J, Sathiyaseelan T, Vargas F (2007) Production of cattle lacking prion protein. Nature Biotechnology 25:132–138CrossRefGoogle Scholar
  126. Robl JM, Wang Z, Kasinathan P, Kuroiwa Y (2007) Transgenic animal production and animal biotechnology. Theriogenology 67:127–133 (epub ahead of print, doi: 10.1016/j.theriogenology.2006.09.034)Google Scholar
  127. Rudenko L, Matheson JC, Sundlof SF (2007) Animal Cloning and the FDA: the risk assessment paradigm under public scrutiny. Nature Biotechnology 25:39–43CrossRefGoogle Scholar
  128. Rossant J (2001) Stem cells from the mammalian blastocyst. Stem Cells 19(6):477–482CrossRefGoogle Scholar
  129. Rudolph NS (1999) Biopharmaceutical production in transgenic livestock. Trends Biotechnol 17(9):367–374CrossRefGoogle Scholar
  130. Saeki K, Matsumoto K, Kinoshita M, Suzuki I, Tasaka Y, Kano K, Taguchi Y, Mikami K, Hirabayashi M, Kashiwazaki N, Hosoi Y, Murata N, Iritani A (2004) Functional expression of a Delta12 fatty acid desaturase gene from spinach in transgenic pigs. Proc Natl Acad Sci USA 101(17):6361–6366CrossRefGoogle Scholar
  131. Schätzlein S, Lucas-Hahn A, Lemme E, Kues WA, Dorsch M, Manns MP, Niemann H, Rudolph KL (2004) Telomere length is reset during early mammalian embryogenesis. Proc Natl Acad Sci USA 101(21):8034–8038CrossRefGoogle Scholar
  132. Schätzlein S, Rudolph KL (2005) Telomere length regulation during cloning, embryogenesis and aging. Reprod Fertil Dev 17(1,2):85–96CrossRefGoogle Scholar
  133. Schnieke AE, Kind AJ, Ritchie WA, Mycock K, Scott AR, Ritchie M, Wilmut I, Colman A, Campbell KH (1997) Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 278(5346):2130–2133CrossRefGoogle Scholar
  134. Shim H, Gutierrez-Adan A, Chen LR, BonDurant RH, Behboodi E, Anderson GB (1997) Isolation of pluripotent stem cells from cultured porcine primordial germ cells. Biol Reprod 57(5):1089–1095CrossRefGoogle Scholar
  135. Staeheli P (1991) Intracellular immunization: a new strategy for producing diseaseresistant transgenic livestock? Trends Biotechnol 9(3):71–72CrossRefGoogle Scholar
  136. Stinnakre MG, Vilotte JL, Soulier S, Mercier JC (1994) Creation and phenotypic analysis of α-lactalbumin-deficient mice. Proc Natl Acad Sci USA 91(14):6544–6548CrossRefGoogle Scholar
  137. Swanson ME, Martin MJ, O’Donnell JK, Hoover K, Lago W, Huntress V, Parsons CT, Pinkert CA, Pilder S, Logan JS (1992) Production of functional human hemoglobin in transgenic swine. Biotechnology 10(5):557–559CrossRefGoogle Scholar
  138. Switzer WM, Michler RE, Shangmugam V, Matthews A, Hussain AI, Wright A, Sandstrom P, Chapman L, Weber C, Safley S, Denny RD, Navarro A, Evans V, Norin AJ, Kwiatkowski P, Heneine W (2001) Lack of cross-species transmission of porcine endogenous retrovirus infection to nonhuman primate recipients of porcine cells, tissues and organs. Transplantation 71:959–965CrossRefGoogle Scholar
  139. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–76CrossRefGoogle Scholar
  140. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872CrossRefGoogle Scholar
  141. Tamashiro KL, Wakayama T, Blanchard RJ, Blanchard DC, Yanagimachi R (2000) Postnatal growth and behavioral development of mice cloned from adult cumulus cells. Biol Reprod 63:328–234CrossRefGoogle Scholar
  142. Templin MF, Stoll D, Schrenk M, Traub PC, Vohringer CF, Joos TO (2002) Protein microarray technology. Trends Biotechnol 20(4):160–166CrossRefGoogle Scholar
  143. Tenenhaus Dann C, Alvarado AL, Hammer RE, Garbers DL (2006) Heritable and stable gene knockdown in rats. Proc Natl Acad Sci USA 103:11246–11251CrossRefGoogle Scholar
  144. Theuring F, Thunecke M, Kosciessa U, Turner JD (1997) Transgenic animals as models of neurodegenerative disease in humans. Trends Biotechnol 15(8):320–325CrossRefGoogle Scholar
  145. Tian XC, Kubota C, Sakashita K, Izaike Y, Okano R, Tabara N, Curchoe C, Jacob L, Zhang Y, Smith S, Bormann C, Xu, J, Sato M, Andrew S, Yang X (2005) Meat and milk compositions of bovine clones. Proceedings National Academy of Sciences USA 102:6261–6266Google Scholar
  146. Tucker A, Belcher C, Moloo B, Bell J, Mazzulli T, Humar Y, Hughes A, McArdle P, Talbot A (2002) The production of transgenic pigs for potential use in clinical xenotransplantation: baseline clinical pathology and organ size studies. Xenotransplantation 9:203–208CrossRefGoogle Scholar
  147. van Berkel PH, Welling MM, Geerts M, van Veen HA, Ravensbergen B, Salaheddine M, Pauwels EK, Pieper F, Nuijens JH, Nibbering PH (2002) Large scale production of recombinant human lactoferrin in the mik of trangenic cows. Nat Biotechnol 20(5):484–487CrossRefGoogle Scholar
  148. Van den Hout JM, Reuser AJ, de Klerk JB, Arts WF, Smeitink JA, Van der Ploeg AT (2001) Enzyme therapy for Pompe disease with recombinant human α-glucosidase from rabbit milk. J Inherit Metab Dis 24(2):266–274CrossRefGoogle Scholar
  149. Van Reenen CG, Meuwissen THE, Hopster H, Oldenbroek K, Kruip TH, Blokhuis HJ (2001) Transgenesis may affect farm animal welfare: a case for systemic risk assessment. J Anim Sci 79:1763–1769Google Scholar
  150. Wakayama T, Shinkai Y, Tamashiro KL, Niida H, Blanchard DC, Blanchard RJ (2000) Cloning of mice to six generations. Nature 407:318–319CrossRefGoogle Scholar
  151. Wall RJ, Powell A, Paape MJ, Kerr DE, Bannermann DD, Pursel VG, Wells KD, Talbot N, Hawk H (2005) Genetically enhanced cows resist intramammary Staphylococcus aureus infection. Nat Biotechnol 23(4):445–451CrossRefGoogle Scholar
  152. Ward KA (2000) Transgene-mediated modifications to animal biochemistry. Trends Biotechnol 18(3):99–102CrossRefGoogle Scholar
  153. Weidle UH, Lenz H, Brem G (1991) Genes encoding a mouse monoclonal antibody are expressed in transgenic mice, rabbits and pigs. Gene 98(2):185–191CrossRefGoogle Scholar
  154. Weissmann C, Enari M, Klohn PC, Rossi D, Flechsig E (2002) Transmission of prions. Proc Natl Acad Sci USA 99(Suppl 4):16378–16383CrossRefGoogle Scholar
  155. Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R. (2007) In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448:318–324CrossRefGoogle Scholar
  156. Wheeler MB (1994) Development and validation of swine embryonic stem cells: a review. Reprod Fertil Dev 6(5):563–568CrossRefGoogle Scholar
  157. Wheeler MB, Bleck GT, Donovan SM (2001) Transgenic alteration of sow milk to improve piglet growth and health. Reproduction Suppl 58:313–324Google Scholar
  158. Whitelaw CB, Radcliffe PA, Ritchie WA, Carlisle A, Ellard FM, Pena RN, Rowe J, Clark AJ, King TJ, Mitrophanous KA (2004) Efficient generation of transgenic pigs using equine infectious anaemia virus (EIAV) derived vector. FEBS Lett 571:233–236CrossRefGoogle Scholar
  159. Willadsen SM (1986) Nuclear transplantation in sheep embryos. Nature 320:63–65CrossRefGoogle Scholar
  160. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385:810–813CrossRefGoogle Scholar
  161. Yang YG and Sykes M (2007) Xenotransplantation: current status and a perspective on the future. Nat Rev Immunol 7(7):519–531CrossRefGoogle Scholar
  162. Yang X, Tian C, Kubota C, Page R, Xu J, Cibelli J (2007) Risk assessment of meat and milk from cloned animals. Nature Biotechnology 25:77–83CrossRefzbMATHGoogle Scholar
  163. Yamada K, Yazawa K, Shimizu A, Iwanaga T, Hisashi Y, Nuhn M, O’Malley P, Nobori S, Vagefi PA, Patience C, Fishman J, Cooper DK, Hawley RJ, Greenstein J, Schuurman HJ, Awwad M, Sykes M, Greenstein J, Schuurman HJ, Awwad M, Sykes M, Sachs DH Sachs DH (2005) Marked prolongation of porcine renal xenograft survival in baboons through the use of α1,3- galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue. Nat Med 11(1):32–34CrossRefGoogle Scholar
  164. Yom HC, Bremel RD (1993) Genetic engineering of milk composition: modification of milk components in lactating transgenic animals. Am J Clin Nutr 58 (Suppl 2):299–306Google Scholar
  165. Ziomek CA (1998) Commercialization of proteins produced in the mammary gland. Theriogenology 49(1):139–144CrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Heiner Niemann
  • Wilfried Kues
  • Joseph W. Carnwath

There are no affiliations available

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