1932

Abstract

Recent advances in the production of genetically engineered (GE) livestock have resulted in a variety of new transgenic animals with desirable production and composition changes. GE animals have been generated to improve growth efficiency, food composition, and disease resistance in domesticated livestock species. GE animals are also used to produce pharmaceuticals and as medical models for human diseases. The potential use of these food animals for human consumption has prompted an intense debate about food safety and animal welfare concerns with the GE approach. Additionally, public perception and ethical concerns about their use have caused delays in establishing a clear and efficient regulatory approval process. Ethically, there are far-reaching implications of not using genetically engineered livestock, at a detriment to both producers and consumers, as use of this technology can improve both human and animal health and welfare.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-animal-022114-110739
2015-02-16
2024-06-14
Loading full text...

Full text loading...

/deliver/fulltext/animal/3/1/annurev-animal-022114-110739.html?itemId=/content/journals/10.1146/annurev-animal-022114-110739&mimeType=html&fmt=ahah

Literature Cited

  1. Cohen SN, Chang AC, Boyer HW, Helling RB. 1973. Construction of biologically functional bacterial plasmids in vitro. Proc. Natl. Acad. Sci. USA 70:113240–44 [Google Scholar]
  2. Morrow JF, Cohen SN, Chang ACY, Boyer HW, Goodman HM, Helling RB. 1974. Replication and transcription of eukaryotic DNA in Esherichia coli. Proc. Natl. Acad. Sci. USA 71:51743–47 [Google Scholar]
  3. Costantini F, Lacy E. 1981. Introduction of a rabbit β-globin gene into the mouse germ line. Nature 294:583692–94 [Google Scholar]
  4. Gordon JW, Ruddle FH. 1981. Integration and stable germ line transmission of genes injected into mouse pronuclei. Science 214:45261244–46 [Google Scholar]
  5. Palmiter RD, Brinster RL, Hammer RE, Trumbauer ME, Rosenfeld MG et al. 1982. Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature 300:5893611–15 [Google Scholar]
  6. Hammer RE, Pursel VG, Rexroad CE, Wall RJ, Bolt DJ et al. 1985. Production of transgenic rabbits, sheep and pigs by microinjection. Nature 315:6021680–83 [Google Scholar]
  7. Wall RJ. 2001. Pronuclear microinjection. Cloning Stem Cells 3:4209–20 [Google Scholar]
  8. Maga EA, Sargent RG, Zeng H, Pati S, Zarling DA et al. 2003. Increased efficiency of transgenic livestock production. Transgenic Res. 12:4485–96 [Google Scholar]
  9. West AG, Gaszner M, Felsenfeld G. 2002. Insulators: many functions, many mechanisms. Genes Dev. 16:3271–88 [Google Scholar]
  10. Thomas KR, Capecchi MR. 1987. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51:3503–12 [Google Scholar]
  11. Whitworth KM, Prather RS. 2010. Somatic cell nuclear transfer efficiency: How can it be improved through nuclear remodeling and reprogramming?. Mol. Reprod. Dev. 77:121001–15 [Google Scholar]
  12. Hofmann A, Kessler B, Ewerling S, Weppert M, Vogg B et al. 2003. Efficient transgenesis in farm animals by lentiviral vectors. EMBO Rep. 4:111054–60 [Google Scholar]
  13. Pfeifer A, Ikawa M, Dayn Y, Verma IM. 2002. Transgenesis by lentiviral vectors: lack of gene silencing in mammalian embryonic stem cells and preimplantation embryos. Proc. Natl. Acad. Sci. USA 99:42140–45 [Google Scholar]
  14. Lois C. 2002. Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science 295:5556868–72 [Google Scholar]
  15. Clark J, Whitelaw B. 2003. A future for transgenic livestock. Nat. Rev. Genet. 4:10825–33 [Google Scholar]
  16. Ritchie WA, King T, Neil C, Carlisle AJ, Lillico S et al. 2009. Transgenic sheep designed for transplantation studies. Mol. Reprod. Dev. 76:161–64 [Google Scholar]
  17. Hofmann A, Kessler B, Ewerling S, Kabermann A, Brem G et al. 2006. Epigenetic regulation of lentiviral transgene vectors in a large animal model. Mol. Ther. 13:159–66 [Google Scholar]
  18. Jabed A, Wagner S, McCracken J, Wells DN, Laible G. 2012. Targeted microRNA expression in dairy cattle directs production of β-lactoglobulin-free, high-casein milk. Proc. Natl. Acad. Sci. USA 109:4216811–16 [Google Scholar]
  19. Tessanne K, Golding MC, Long CR, Peoples MD, Hannon G, Westhusin ME. 2011. Production of transgenic calves expressing an shRNA targeting myostatin. Mol. Reprod. Dev. 79:3176–85 [Google Scholar]
  20. Lyall J, Irvine RM, Sherman A, McKinley TJ, Núñez A et al. 2011. Suppression of avian influenza transmission in genetically modified chickens. Science 331:6014223–26 [Google Scholar]
  21. Carlson DF, Tan W, Lillico SG, Stverakova D, Proudfoot C et al. 2012. Efficient TALEN-mediated gene knockout in livestock. Proc. Natl. Acad. Sci. USA 109:4317382–87 [Google Scholar]
  22. Lillico SG, Proudfoot C, Carlson DF, Stverakova D, Neil C et al. 2013. Live pigs produced from genome edited zygotes. Sci. Rep 3:2847 [Google Scholar]
  23. Hai T, Teng F, Guo R, Li W, Zhou Q. 2014. One-step generation of knockout pigs by zygote injection of CRISPR/Cas system. Cell Res 24:3372–75 [Google Scholar]
  24. Kues WA, Niemann H. 2011. Advances in farm animal transgenesis. Prev. Vet. Med. 102:2146–56 [Google Scholar]
  25. Bleck GT, White BR, Miller DJ, Wheeler MB. 1998. Production of bovine alpha-lactalbumin in the milk of transgenic pigs. J. Anim. Sci 76:123072–78 [Google Scholar]
  26. Pursel VG, Mitchell AD, Bee G, Elsasser TH, McMurtry JP et al. 2004. Growth and tissue accretion rates of swine expressing an insulin-like growth factor I transgene. Anim. Biotechnol. 15:133–45 [Google Scholar]
  27. Damak S, Su H, Jay NP, Bullock DW. 1996. Improved wool production in transgenic sheep expressing insulin-like growth factor 1. Biotechnology 14:2185–88 [Google Scholar]
  28. Su HY, Jay NP, Gourley TS, Kay GW, Damak S. 1998. Wool production in transgenic sheep: results from first-generation adults and second-generation lambs. Anim. Biotechnol 9:2135–47 [Google Scholar]
  29. Brophy B, Smolenski G, Wheeler T, Wells D, L'Huillier P, Laible G. 2003. Cloned transgenic cattle produce milk with higher levels of β-casein and κ-casein. Nat. Biotechnol 21:2157–62 [Google Scholar]
  30. Du SJ, Gong ZY, Fletcher GL, Shears MA, King MJ et al. 1992. Growth enhancement in transgenic Atlantic salmon by the use of an “all fish” chimeric growth hormone gene construct. Nat. Biotechnol 10:2176–81 [Google Scholar]
  31. Smith MD, Asche F, Guttormsen AG, Wiener JB. 2010. Food safety. Genetically modified salmon and full impact assessment. Science 330:60071052–53 [Google Scholar]
  32. Saeki K, Matsumoto K, Kinoshita M, Suzuki I, Tasaka Y et al. 2004. Functional expression of a Δ12 fatty acid desaturase gene from spinach in transgenic pigs. Proc. Natl. Acad. Sci. USA 101:176361–66 [Google Scholar]
  33. Lai L, Kang JX, Li R, Wang J, Witt WT et al. 2006. Generation of cloned transgenic pigs rich in omega-3 fatty acids. Nat. Biotechnol. 24:4435–36 [Google Scholar]
  34. Reh WA, Maga EA, Collette NMB, Moyer A, Conrad-Brink JS et al. 2004. Hot topic: using a stearoyl-CoA desaturase transgene to alter milk fatty acid composition. J. Dairy Sci. 87:103510–14 [Google Scholar]
  35. Prather RS, Shen M, Dai Y. 2008. Genetically modified pigs for medicine and agriculture. Biotechnol. Genet. Eng. Rev. 25:245–65 [Google Scholar]
  36. Maga EA, Shoemaker CF, Rowe JD, BonDurant RH, Anderson GB, Murray JD. 2006. Production and processing of milk from transgenic goats expressing human lysozyme in the mammary gland. J. Dairy Sci. 89:2518–24 [Google Scholar]
  37. Maga EA, Cullor JS, Smith W, Anderson GB, Murray JD. 2006. Human lysozyme expressed in the mammary gland of transgenic dairy goats can inhibit the growth of bacteria that cause mastitis and the cold-spoilage of milk. Foodborne Pathog. Dis. 3:4384–92 [Google Scholar]
  38. Maga EA, Walker RL, Anderson GB, Murray JD. 2006. Consumption of milk from transgenic goats expressing human lysozyme in the mammary gland results in the modulation of intestinal microflora. Transgenic Res. 15:4515–19 [Google Scholar]
  39. Maga EA, Desai PT, Weimer BC, Dao N, Kültz D, Murray JD. 2012. Consumption of lysozyme-rich milk can alter microbial fecal populations. Appl. Environ. Microbiol. 78:176153–60 [Google Scholar]
  40. Cooper CA, Garas Klobas LC, Maga EA, Murray JD. 2013. Consuming transgenic goats’ milk containing the antimicrobial protein lysozyme helps resolve diarrhea in young pigs. PLOS ONE 8:3e58409 [Google Scholar]
  41. van Berkel PHC, Welling MM, Geerts M, van Veen HA, Ravensbergen B et al. 2002. Large scale production of recombinant human lactoferrin in the milk of transgenic cows. Nat. Biotechnol. 20:5484–87 [Google Scholar]
  42. Cooper CA, Nelson KM, Maga EA, Murray JD. 2012. Consumption of transgenic cows' milk containing human lactoferrin results in beneficial changes in the gastrointestinal tract and systemic health of young pigs. Transgenic Res 22:571–78 [Google Scholar]
  43. Wall RJ, Powell AM, Paape MJ, Kerr DE, Bannerman DD et al. 2005. Genetically enhanced cows resist intramammary Staphylococcus aureus infection. Nat. Biotechnol 23:4445–51 [Google Scholar]
  44. Müller M, Brenig B, Winnacker E-L, Brem G. 1992. Transgenic pigs carrying cDNA copies encoding the murine Mx1 protein which confers resistance to influenza virus infection. Gene 121:2263–70 [Google Scholar]
  45. Lo D, Pursel V, Linton PJ, Sandgren E, Behringer R et al. 1991. Expression of mouse IgA by transgenic mice, pigs and sheep. Eur. J. Immunol. 21:41001–6 [Google Scholar]
  46. Richt JA, Kasinathan P, Hamir AN, Castilla J, Sathiyaseelan T et al. 2007. Production of cattle lacking prion protein. Nat. Biotechnol. 25:1132–38 [Google Scholar]
  47. Whitelaw CBA, Sang HM. 2005. Disease-resistant genetically modified animals. Rev. Sci. Tech. Off. Int. Epizoot. 24:1275–83 [Google Scholar]
  48. Tilman D, Cassman KG, Matson PA, Naylor R, Polasky S. 2002. Agricultural sustainability and intensive production practices. Nature 418:6898671–77 [Google Scholar]
  49. Natl. Res. Counc. 2012. Nutrient Requirements of Swine. Washington, DC: Natl. Acad. Press. 391 pp. 11th ed
  50. Jongbloed AW, Lenis NP. 1998. Environmental concerns about animal manure. J. Anim. Sci 76:102641–48 [Google Scholar]
  51. Golovan SP, Meidinger RG, Ajakaiye A, Cottrill M, Wiederkehr MZ et al. 2001. Pigs expressing salivary phytase produce low-phosphorus manure. Nat. Biotechnol. 19:8741–45 [Google Scholar]
  52. Edmunds T, Van Patten SM, Pollock J, Hanson E, Bernasconi R et al. 1998. Transgenically produced human antithrombin: structural and functional comparison to human plasma-derived antithrombin. Blood 91:124561–71 [Google Scholar]
  53. Houdebine LM. 2009. Production of pharmaceutical proteins by transgenic animals. Comp. Immunol. Microbiol. Infect. Dis. 32:2107–21 [Google Scholar]
  54. Rapp JC, Harvey AJ, Speksnijder GL, Hu W, Ivarie R. 2003. Biologically active human interferon α-2b produced in the egg white of transgenic hens. Transgenic Res. 12:5569–75 [Google Scholar]
  55. Zhu L, van de Lavoir M-C, Albanese J, Beenhouwer DO, Cardarelli PM et al. 2005. Production of human monoclonal antibody in eggs of chimeric chickens. Nat. Biotechnol. 23:91159–69 [Google Scholar]
  56. Penno CA, Kawabe Y, Ito A, Kamihira M. 2009. Production of recombinant human erythropoietin/Fc fusion protein by genetically manipulated chickens. Transgenic Res. 19:2187–95 [Google Scholar]
  57. Ramsoondar JJ, Macháty Z, Costa C, Williams BL, Fodor WL, Bondioli KR. 2003. Production of α1,3-galactosyltransferase-knockout cloned pigs expressing human α1,2-fucosylosyltransferase. Biol. Reprod. 69:2437–45 [Google Scholar]
  58. Fujimura T, Kurome M, Murakami H, Takahagi Y, Matsunami K et al. 2004. Cloning of the transgenic pigs expressing human decay accelerating factor and N-acetylglucosaminyltransferase III. Cloning Stem Cells 6:3294–301 [Google Scholar]
  59. Klymiuk N, Aigner B, Brem G, Wolf E. 2009. Genetic modification of pigs as organ donors for xenotransplantation. Mol. Reprod. Dev. 77:3209–21 [Google Scholar]
  60. Whyte JJ, Prather RS. 2011. Genetic modifications of pigs for medicine and agriculture. Mol. Reprod. Dev. 78:10–11879–91 [Google Scholar]
  61. 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 15:136–45 [Google Scholar]
  62. Gock H, Nottle M, Lew AM, d'Apice AJF, Cowan P. 2011. Genetic modification of pigs for solid organ xenotransplantation. Transplant. Rev 25:19–20 [Google Scholar]
  63. Kobayashi T, Yamaguchi T, Hamanaka S, Kato-Itoh M, Yamazaki Y et al. 2010. Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells. Cell 142:5787–99 [Google Scholar]
  64. Usui J-I, Kobayashi T, Yamaguchi T, Knisely AS, Nishinakamura R, Nakauchi H. 2012. Generation of kidney from pluripotent stem cells via blastocyst complementation. Am. J. Pathol. 180:62417–26 [Google Scholar]
  65. Matsunari H, Nagashima H, Watanabe M, Umeyama K, Nakano K et al. 2013. Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs. Proc. Natl. Acad. Sci. USA 110:124557–62 [Google Scholar]
  66. Luo Y, Lin L, Bolund L, Jensen TG, Sørensen CB. 2012. Genetically modified pigs for biomedical research. J. Inherit. Metab. Dis. 35:4695–713 [Google Scholar]
  67. Baxa M, Hruska-Plochan M, Juhas S, Vodicka P, Pavlok A et al. 2013. A transgenic minipig model of Huntington's disease. J. Huntingt. Dis. 2:47–68 [Google Scholar]
  68. Jacobsen JC, Bawden CS, Rudiger SR, McLaughlan CJ, Reid SJ et al. 2010. An ovine transgenic Huntington's disease model. Hum. Mol. Genet. 19:101873–82 [Google Scholar]
  69. Stoltz DA, Meyerholz DK, Pezzulo AA, Ramachandran S, Rogan MP et al. 2010. Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth. Sci. Transl. Med. 2:2929ra31 [Google Scholar]
  70. Widdicombe JH. 2010. Transgenic animals may help resolve a sticky situation in cystic fibrosis. J. Clin. Investig. 120:93093–96 [Google Scholar]
  71. Whyte JJ, Samuel M, Mahan E, Padilla J, Simmons GH et al. 2011. Vascular endothelium-specific overexpression of human catalase in cloned pigs. Transgenic Res. 20:5989–1001 [Google Scholar]
  72. Whyte J, Laughlin MH. 2010. Placentation in the pig visualized by eGFP fluorescence in eNOS over-expressing cloned transgenic swine. Mol. Reprod. Dev. 77:7565 [Google Scholar]
  73. Polejaeva IA, Hall J, Meng Q, Zhou X, Sessions BR et al. 2012. Development of a transgenic goat model with cardiac-specific overexpression of transforming growth factor-β1 to study the relationship between atrial fibrosis and atrial fibrillation. Circ. Res. 11:4A251 [Google Scholar]
  74. US Food Drug Adm. 2011. Guidance for Industry #187: Regulation of Genetically Engineered Animals Containing Heritable Recombinant DNA Constructs. Washington, DC: US Food Drug Adm. http://www.fda.gov/downloads/AnimalVeterinary/GuidanceCompliance Enforcement/GuidanceforIndustry/UCM113903.pdf
  75. Int. Food Inf. Counc. 2012. 2012 “Consumer Perceptions of Food Technology” Survey. Washington, DC: Int. Food Inf. Counc. http://www.foodinsight.org–Content–5438–FINAL%20Executive%20Summary%205–8–12.pdf
  76. Abrahams MV, Sutterlin A. 1999. The foraging and antipredator behaviour of growth-enhanced transgenic Atlantic salmon. Anim. Behav 58:5933–42 [Google Scholar]
  77. Jackson KA, Berg JM, Murray JD, Maga EA. 2010. Evaluating the fitness of human lysozyme transgenic dairy goats: growth and reproductive traits. Transgenic Res 19:6977–86 [Google Scholar]
  78. Clark M, Murray JD, Maga EA. 2014. Assessing unintended effects of a mammary-specific transgene at the whole animal level in host and non-target animals. Transgenic Res 23:245–56 [Google Scholar]
  79. Rollin BE. 2014. Telos, conservation of welfare, and ethical issues in genetic engineering of animals. Curr. Top. Behav. Neurosci In press [Google Scholar]
/content/journals/10.1146/annurev-animal-022114-110739
Loading
/content/journals/10.1146/annurev-animal-022114-110739
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error