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Regulatory Dysfunction inhibits the Development and Application of Transgenic Livestock for Use in Agriculture

  • James D. Murray
  • Elizabeth A. Maga
Chapter

Abstract

Since the production of the first transgenic livestock, the technology for producing the animals and controlling transgene expression has matured. Initially, the lack of knowledge about promoter, enhancer, and coding regions of genes of interest greatly hampered efforts to create transgenes that would express appropriately in livestock and be useful to industry. There have been many developments in the technology to create transgenic animals, including somatic cell nuclear transfer-based cloning and gene editing. In the 31 years since the first report of transgenic livestock, a number of potentially useful animals, including cattle, goats, pigs, and sheep, have been made. However, there still are no genetically engineered animal-based food products on the market. There has been a failure of the regulatory processes to effectively move forward across the world, with many countries adopting process-based regulations, rather than product-based, and some countries having no regulatory framework at all. Additionally, there is a perception among some consumers that transgenic technology is potentially harmful in spite of a large, and growing, body of evidence to the contrary. Estimates suggest the world will need to approximately double our current food production by 2050, including animal-based foods; that is, we will have to produce an amount of food each year equal to that consumed by mankind over the past 500 years. The practical benefits of transgenic animals in agriculture have not yet reached consumers, and in the absence of predictable, science-based regulatory programs, it is unlikely that the benefits will be realized in the short to medium term.

Keywords

Transgenic livestock Agriculture Regulation Regulatory dysfunction Genetic engineering, GE Transgenic pigs Transgenic cattle Transgenic goats 

References

  1. Archibald AL, McClenaghan M, Hornsey V, Simons JP, Clark AJ (1990) High-level expression of biologically active human alpha 1-antitrypsin in the milk of transgenic mice. Proc Natl Acad Sci U S A 87:5178–5182PubMedPubMedCentralCrossRefGoogle Scholar
  2. Bawden CS, Powell BC, Walker SK, Rogers GE (1998) Expression of a wool intermediate filament keratin transgene in sheep fibre alters structure. Transgenic Res 7:273–287PubMedCrossRefPubMedCentralGoogle Scholar
  3. 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 milk of transgenic cows. Nat Biotechnol 20:484–487PubMedCrossRefPubMedCentralGoogle Scholar
  4. Bleck GT, White BR, Miller DJ, Wheeler MB (1998) Production of bovine α-lactalbumin in the milk of transgenic pigs. J Anim Sci 76:3072–3078PubMedCrossRefPubMedCentralGoogle Scholar
  5. Boch J, Scholze H, Schornack S, Landgraf A, Hahn S, Kay S, Lahaye T, Nickstadt A, Bonas U (2009) Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326:1509–1512PubMedCrossRefPubMedCentralGoogle Scholar
  6. Bowen RA, Reed ML, Schnieke A, Seidel GE Jr, Stacey A, Thomas WK, Kajikawa O (1994) Transgenic cattle resulting from biopsied embryos: expression of c-ski in a transgenic calf. Biol Reprod 50:664–668PubMedCrossRefPubMedCentralGoogle Scholar
  7. Brem G, Brenig B, Goodman HM, Selden RC, Graf F, Kruff B et al (1985) Production of transgenic mice, rabbits and pigs by microinjection into pronuclei. Zuchthygiene 20:251–252CrossRefGoogle Scholar
  8. Brophy B, Smolenski G, Wheeler T, Wells D, L’Huillier P, Laible G (2003) Cloned transgenic cattle produce milk with higher levels of beta-casein and kappacasein. Nat Biotechnol 21:157–162PubMedCrossRefPubMedCentralGoogle Scholar
  9. Brundige DR, Maga EA, Klasing KC, Murray JD (2008) Lysozyme transgenic goats’ milk influences gastrointestinal morphology in young pigs. J Nutr 138:921–926PubMedCrossRefPubMedCentralGoogle Scholar
  10. Brundige DR, Maga EA, Klasing KC, Murray JD (2010) Consumption of pasteurized human lysozyme transgenic goats’ milk alters serum metabolite profile in young pigs. Transgenic Res 19:563–574PubMedCrossRefPubMedCentralGoogle Scholar
  11. Campbell KH, McWhir J, Ritchie WA, Wilmut I (1996) Sheep cloned by nuclear transfer from a cultured cell line. Nature 380:64–68PubMedCrossRefPubMedCentralGoogle Scholar
  12. Carneiro IS, Menezes JNR, Maia JA, Miranda AM, Oliveira VBS, Murray JD, Maga EA, Bertolini M, Bertolini LR (2018) Milk from transgenic goat expressing human lysozyme for recovery and treatment of gastrointestinal pathogens. Eur J Pharm Sci 112:79–86PubMedCrossRefPubMedCentralGoogle Scholar
  13. Carvalho EB, Maga EA, Quetz JS, Lima IFN, Magalhaes HYF, Rodrigues FAR, Silva AVA, Prata MMG, Cavalcante PA, Havt A, Bertolini M, Bertolini LR, Lima AAM (2012) Goat milk with and without increased concentrations of lysozyme improves repair of intestinal cell damage induced by enteroaggregative Escherichia coli. BMC Gastroenterol 12:106PubMedPubMedCentralCrossRefGoogle Scholar
  14. Cibelli JB, Stice SL, Golueke PJ, Kane JJ, Jerry J, Blackwell C, Ponce de León FA, Robl JM (1998) Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science 280:1256–1258PubMedCrossRefPubMedCentralGoogle Scholar
  15. 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 23:245–256PubMedCrossRefPubMedCentralGoogle Scholar
  16. Clements JE, Wall RJ, Narayan O, Hauer D, Schoborg R, Sheffer D et al (1994) Development of transgenic sheep that express the visna virus envelope gene. Virology 200:370–380PubMedCrossRefPubMedCentralGoogle Scholar
  17. Cooper CA, Brundige DR, Reh WA, Maga EA, Murray JD (2011) Lysozyme transgenic goats’ milk positively impacts intestinal cytokine expression and morphology. Transgenic Res 20:1235–1243PubMedPubMedCentralCrossRefGoogle Scholar
  18. 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 22:571–578PubMedCrossRefPubMedCentralGoogle Scholar
  19. Cooper CA, Garas Klobas L, Maga EA, Murray JD (2013) Consuming transgenic goats’ milk containing the antimicrobial protein lysozyme helps resolve diarrhea in young pigs. PLoS One 8:e58409PubMedPubMedCentralCrossRefGoogle Scholar
  20. Cooper CA, Maga EA, Murray JD (2014a) Consumption of transgenic milk containing the antimicrobials lactoferrin and lysozyme separately and in conjunction by 6 week old pigs improves intestinal and systemic health. J Dairy Res 81:30–37PubMedCrossRefGoogle Scholar
  21. Cooper CA, Nonnecke E, Lonnerdal B, Murray JD (2014b) The lactoferrin receptor may mediate the reduction of eosinophils in the duodenum of pigs consuming milk containing recombinant human lactoferrin. Biometals 27:1031–1038.  https://doi.org/10.1007/s10534-014-9778-8 CrossRefPubMedGoogle Scholar
  22. Cooper CA, Maga EA, Murray JD (2015) Production of human lactoferrin and lysozyme in the milk of transgenic dairy animals: past, present and future. Transgenic Res 24:605–614.  https://doi.org/10.1007/s11248-015-9885-5 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Dai Y, Vaught TD, Boone J, Chen S-H 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 20:251–255PubMedCrossRefPubMedCentralGoogle Scholar
  24. Damak S, Jay NP, Barrell GK, Bullock DW (1996a) Targeting gene expression to the wool follicle in transgenic sheep. Biotechnology 14:181–184PubMedPubMedCentralGoogle Scholar
  25. Damak S, Su H, Jay NP, Bullock DW (1996b) Improved wool production in transgenic sheep expressing insulin-like growth factor 1. Biotechnology 14:185–188PubMedPubMedCentralGoogle 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 |[alpha]|(1,3)galactosyl transferase (GGTA1) gene and the prion protein (PrP) gene in sheep. Nat Biotechnol 19:559–562PubMedCrossRefGoogle Scholar
  27. Ding S, Wu X, Li G, Han M, Zhuang Y, Xu T (2005) Efficient transposition of the piggyBac (PB) transposon in mammalian cells and mice. Cell 122:473–483PubMedCrossRefPubMedCentralGoogle Scholar
  28. Durai S, Mani M, Kandavelou K, Wu J, Porteus MH, Chandrasegaran S (2005) Zinc finger nucleases: custom-designed molecular scissors for genome engineering of plant and mammalian cells. Nucleic Acids Res 33:5978–5990PubMedPubMedCentralCrossRefGoogle Scholar
  29. Ebert KM, Low MJ, Overstrom EW, Buonomo FC, Baile CA, Roberts TM et al (1988) A Moloney MLV-rat somatotropin fusion gene produces biologically active somatotropin in a transgenic pig. Mol Endocrinol 2:277–283PubMedCrossRefPubMedCentralGoogle Scholar
  30. Ebert KM, Smith TE, Buonoma FC, Overstrom EW, Low EJ (1990) Porcine growth hormone gene expression from viral promoters in transgenic swine. Anim Biotechnol 1:145–159CrossRefGoogle Scholar
  31. Ebert KM, DiTullio P, Barry CA, Schindler JE, Ayres SL, Smith TE, Pellerin LJ, Meade HM, Denman J, Roberts B (1994) Induction of human tissue plasminogen activator in the mammary gland of transgenic goats. Bio/Technology 12:699–702PubMedPubMedCentralGoogle Scholar
  32. Fahrenkrug SC, Blake A, Carlson DF, Doran T, Van Eenennaam A, Faber D, Galli C, Hackett PB, Li N, Maga EA, Murray JD, Stotish R, Sullivan E, Taylor JF, Walton M, Wheeler M, Whitelaw B, Glenn BP (2010) Precision genetics for complex objectives in animal agriculture. J Anim Sci 88:2530–2539PubMedCrossRefPubMedCentralGoogle Scholar
  33. FDA (2009) Guidance 187: regulation of genetically engineered animals containing heritable recombinant DNA constructs. www.fda.gov/RegulatoryInformation/Guidances/default.htm
  34. Flisikowska T, Thorey IS, Offner S, Ros F, Lifke V, Zeitler B, Rottmann O, Vincent A, Zhang L, Jenkins S, Niersbach H, Kind AJ, Gregory PD, Schnieke AE, Platzer J (2011) Efficient immunoglobulin gene disruption and targeted replacement in rabbit using zinc finger nucleases. PLoS One 6:e21045.  https://doi.org/10.1371/journal.pone.0021045 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Forsberg CW (2001) Pigs expressing salivary phytase produce low-phosphorus manure. Nat Biotechnol 19:741–745PubMedCrossRefPubMedCentralGoogle Scholar
  36. Forsberg CW, Phillips JP, Golovan SP, Fan MZ, Meidinger RG, Ajakaiye A, Hilborn D, Hacker RR (2003) The Enviropig physiology, performance, and contribution to nutrient management advances in a regulated environment: the leading edge of change in the pork industry12. J Anim Sci 81:E68–E77.  https://doi.org/10.2527/2003.8114_suppl_2E68x CrossRefGoogle Scholar
  37. Forsberg CW, Meidinger RG, Liu M, Cottrill M, Golovan S, Phillips JP (2013) Integration, stability and expression of the E. coli phytase transgene in the Cassie line of Yorkshire Enviropig™. Transgenic Res 22:379–389PubMedCrossRefPubMedCentralGoogle Scholar
  38. Forsberg CW, Meidinger RG, Ajakaiye A, Murray D, Fan MZ, Mandell IB, Phillips JP (2014a) Comparative carcass and tissue nutrient composition of transgenic Yorkshire pigs expressing phytase in the saliva and conventional Yorkshire pigs. J Anim Sci 92:4417–4439PubMedCrossRefPubMedCentralGoogle Scholar
  39. Forsberg CW, Meidinger RG, Murray D, Keirstead ND, Hayes MA, Fan MZ, Ganeshapillai J, Monteiro MA, Golovan SP, Phillips JP (2014b) Phytase properties and locations in tissues of transgenic pigs secreting phytase in the saliva. J Anim Sci 92:3375–3387PubMedCrossRefPubMedCentralGoogle Scholar
  40. Garas L, Murray JD, Maga EA (2015) Genetically engineered livestock: ethical use for food and medical models. Annu Rev Anim Biosci 3:1.1–1.17.  https://doi.org/10.1146/annurev-animal-022114-110739 CrossRefGoogle Scholar
  41. Garas LC, Feltrin C, Hamilton MK, Hagey JV, Murray JD, Bertolini LR, Bertolini M, Raybould HE, Maga EA (2016) Milk with and without lactoferrin can influence intestinal damage in a pig model of malnutrition. Food Funct 7:665–678PubMedCrossRefPubMedCentralGoogle Scholar
  42. Garas LC, Cooper CA, Dawson MW, Wang J-L, Murray JD, Maga EA (2017) Young pigs consuming lysozyme transgenic goat milk are protected from clinical symptoms of enterotoxigenic E. coli infection. J. Nutrition 147:2050–2059.  https://doi.org/10.3945/jn.117.251322 CrossRefGoogle Scholar
  43. Golovan SP, Meidinger RG, Ajakaiye A, Cottrill M, Wiederkehr MZ, Barney DJ, Plante C, Pollard JW, Fan MZ, Anthony Hayes M, Laursen J, Peter Hjorth J, Hacker RR, Phillips JP, Forsberg CW (2001) Pigs expressing salivary phytase produce low-phosphorus manure. Nat Biotechnol 19:741–745Google Scholar
  44. Gordon JW, Scangos GA, Plotkin DJ, Barbosa JA, Ruddle FH (1980) Genetic transformation of mouse embryos by microinjection of purified DNA. Proc Natl Acad Sci U S A 77:7380–7384PubMedPubMedCentralCrossRefGoogle Scholar
  45. Guo T, Liu XF, Ding XB, Yang FF, Nie YW, An YJ, Guo H (2011) Fat-1 transgenic cattle as a model to study the function of ω-3 fatty acids. Lipids Health Dis 10:244–253.  https://doi.org/10.1186/1476-511X-10-244 CrossRefPubMedPubMedCentralGoogle 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 315:680–683PubMedCrossRefPubMedCentralGoogle Scholar
  47. Hartke JL, Monaco MH, Wheeler MB, Donovan SM (2005) Effect of a short-term fast on intestinal disaccharidase activity and villus morphology of piglets suckling insulin-like growth factor-I transgenic sows1. J An Sci 83:2404–2413.  https://doi.org/10.2527/2005.83102404x CrossRefGoogle Scholar
  48. Haskell RE, Bowen RA (1995) Efficient production of transgenic cattle by retroviral infection of early embryos. Mol Reprod Dev 40:386–390PubMedCrossRefPubMedCentralGoogle Scholar
  49. Hu S, Ni W, Sai W, Zi H, Qiao J, Wang P, Sheng J, Chen C (2013) Knockdown of myostatin expression by RNAi enhances muscle growth in transgenic sheep. PLoS One 8(3):e58521.  https://doi.org/10.1371/journal.pone.0058521 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Ivics Z, Hackett PB, Plasterk RH, Izsvák Z (1997) Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell 91:501–510PubMedCrossRefPubMedCentralGoogle Scholar
  51. 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 U S A 109:16811–16816PubMedPubMedCentralCrossRefGoogle Scholar
  52. Jackson KA, Berg JM, Murray JD, Maga EA (2010) Evaluating the fitness of human lysozyme transgenic dairy goats: growth and reproductive traits. Transgenic Res 19:977–986PubMedPubMedCentralCrossRefGoogle Scholar
  53. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–821CrossRefGoogle Scholar
  54. Krimpenfort P, Rademakers A, Eyestone W, van der Schans A, van den Broek S, Kooiman P et al (1991) Generation of transgenic dairy cattle using ‘in vitro’ embryo production. Bio/Technology 9:844–847PubMedPubMedCentralGoogle Scholar
  55. Kues WA, Niemann H (2011) Advances in farm animal transgenesis. Prev Vet Med 102:146–156PubMedCrossRefPubMedCentralGoogle Scholar
  56. 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 24:435–436PubMedPubMedCentralCrossRefGoogle Scholar
  57. Lavitrano M, Forni M, Varzi V, Pucci L, Bacci ML, Di Stefano C, Fioretti D, Zoraqi G, Moioli B, Rossi M, Lazzereschi D, Stoppacciaro A, Seren E, Alfani D, Cortesini R, Frati L (1997) Sperm-mediated gene transfer: production of pigs transgenic for a human regulator of complement activation. Transplant Proc 29:3508–3509PubMedCrossRefPubMedCentralGoogle Scholar
  58. Lee CS, Lee DS, Fang NZ, Oh KB, Shin ST, Lee KK (2006) Integration and expression of goat b-casein/hGH hybrid gene in a transgenic goat. Reprod Dev Biol 30:293–299Google Scholar
  59. Li L, Li Q, Bao Y, Li J, Chen Z, Yu X, Zhao Y, Tian Y, Li N (2014) RNAi-based inhibition of porcine reproductive and respiratory syndrome virus replication in transgenic pigs. J Biotechnol 171:17–24PubMedCrossRefPubMedCentralGoogle Scholar
  60. Laible G (2009) Enhancing livestock through genetic engineering – recent advances and future prospects. Comp Immunol Microbiol Infect Dis 32:123–137Google Scholar
  61. Liu X, Pang D, Yuan T, Li Z, Li Z, Zhang M, Ren W, Ouyang H, Tang X (2016) N-3 polyunsaturated fatty acids attenuates triglyceride and inflammatory factors level in hfat-1 transgenic pigs. Lipids Health Dis 15:89–96PubMedPubMedCentralCrossRefGoogle Scholar
  62. Lu KH, Gordon I, Gallagher M, McGovern H (1987) Pregnancy established in cattle by transfer of embryos derived from in vitro fertilisation of oocytes matured in vitro. Vet Rec 121:259–260PubMedCrossRefPubMedCentralGoogle Scholar
  63. Maga EA, Murray JD (1995) Mammary gland expression of transgenes and the potential for altering the properties of milk. Bio/Technology 13:1452–1457PubMedPubMedCentralGoogle Scholar
  64. Maga EA, Murray JD (2010) Welfare applications of genetically engineered animals for use in agriculture. J An Sci 88:1588–1591CrossRefGoogle Scholar
  65. Maga EA, Sargent RG, Zeng H, Pati S, Zarling DA, Oppenheim SM, Collette NMB, Moyer AL, Conrad-Brink JS, Rowe JD, RH BD, Anderson GB, Murray JD (2003) Increased efficiency of transgenic livestock production. Transgenic Res 12:485–496PubMedCrossRefPubMedCentralGoogle Scholar
  66. Maga EA, Shoemaker CF, Rowe JD, BonDurant RH, Anderson GB, Murray JD (2006a) Production and processing of milk from transgenic goats expressing human lysozyme in the mammary gland. J Dairy Sci 89:518–524PubMedCrossRefPubMedCentralGoogle Scholar
  67. Maga EA, Cullor JS, Smith W, Anderson GB, Murray JD (2006b) 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 3:384–392PubMedCrossRefPubMedCentralGoogle Scholar
  68. Maga EA, Walker RL, Anderson GB, Murray JD (2006c) Consumption of milk from transgenic goats expressing human lysozyme in the mammary gland results in the modulation of intestinal microflora. Transgenic Res 15:515–519PubMedCrossRefPubMedCentralGoogle Scholar
  69. 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 78:6153–6160PubMedPubMedCentralCrossRefGoogle Scholar
  70. Marshall KM, Hurley WL, Shanks RD, Wheeler MB (2006) Effects of suckling intensity on milk yield and piglet growth from lactation-enhanced gilts. J An Sci 84:2346–2351.  https://doi.org/10.2527/jas.2005-764 CrossRefGoogle Scholar
  71. McInnis EA, Kalanetra KM, Mills DA, Maga EA (2015) Analysis of raw goat milk microbiota: impact of stage of lactation and lysozyme on microbial diversity. Food Microbiol 46:121–131PubMedCrossRefPubMedCentralGoogle Scholar
  72. McKnight RA, Shamay A, Sankaran L, Wall RJ, Hennighausen L (1992) Matrix-attachment regions can impart position-independent regulation of a tissue-specific gene in transgenic mice. Proc Natl Acad Sci U S A 89:6943–6947PubMedPubMedCentralCrossRefGoogle Scholar
  73. Meidinger RG, Ajakaiye A, Fan MZ, Zhang J, Phillips JP, Forsberg CW (2013) Digestive utilization of phosphorus from plant-based diets in the Cassie line of transgenic Yorkshire pigs that secrete phytase in the saliva. J Anim Sci 91:1307–1320PubMedCrossRefPubMedCentralGoogle Scholar
  74. Miller KF, Bolt DJ, Pursel VG, Hammer RE, Pinkert CA, Palmiter RD et al (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 120:481–488PubMedCrossRefPubMedCentralGoogle Scholar
  75. Monaco MH, Gronlund DE, Bleck GT, Hurley WL, Wheeler MB, Donovan SM (2005) Mammary specific transgenic over-expression of insulin-like growth factor-I (IGF-I) increases pig milk IGF-I and IGF binding proteins, with no effect on milk composition or yield. Transgenic Res 14:761–773PubMedCrossRefPubMedCentralGoogle Scholar
  76. Moscou MJ, Bogdanove AJ (2009) A simple cipher governs DNA recognition by TAL effectors. Science 326:1501PubMedCrossRefGoogle Scholar
  77. Murray JD, Maga EA (1999) Changing the composition and properties of milk. In: Murray JD, Anderson GB, Oberbauer AM, McGloughlin MM (eds) Transgenic animals in agriculture. CAB International, Wallingham, pp 193–208Google Scholar
  78. Murray JD, Maga EA (2010) Is there a risk from not using GE animals? Transgenic Res 19:357–361PubMedCrossRefPubMedCentralGoogle Scholar
  79. Murray JD, Maga EA (2016a) Genetically engineered livestock for agriculture: a generation after the first transgenic animal research conference. Transgenic Res 25:321–327PubMedCrossRefPubMedCentralGoogle Scholar
  80. Murray JD, Maga EA (2016b) A new paradigm for regulating genetically engineered animals that are used as food. Proc Natl Acad Sci U S A 113:3410–3413.  https://doi.org/10.1073/pnas.1602474113 CrossRefPubMedPubMedCentralGoogle Scholar
  81. Murray JD, Nancarrow CD, Marshall JT, Hazelton IG, Ward KA (1989) Production of transgenic merino sheep by microinjection of ovine metallothioneinovine growth hormone fusion genes. Reprod Fertil Dev 1:147–155PubMedCrossRefPubMedCentralGoogle Scholar
  82. Naldini L, Bloemer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, Trono D (1996) In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272:263–267PubMedCrossRefPubMedCentralGoogle Scholar
  83. Nancarrow CD, Murray JD, Boland MP, Sutton R, Hazelton IG (1984) Effect of gonadotrophin releasing hormone in the production of single‑cell embryos for pronuclear injection of foreign genes. In: Lindsay DR, Pearce DT (eds) Reproduction in sheep. Aust Acad Sci, Canberra, ACT, pp 286–288Google Scholar
  84. Nancarrow CD, Marshall JTA, Clarkson JL, Murray JD, Millard RM, Shanahan CM, Wynn PC, Ward KA (1991) Expression and physiology of performance regulating genes in transgenic sheep. J Reprod Fertil Suppl 43:277–291PubMedPubMedCentralGoogle Scholar
  85. Noble MS, Rodriguez-Zas S, Cook JB, Bleck GT, Hurley WL, Wheeler MB (2002) Lactational performance of first-parity transgenic gilts expressing bovine alpha-lactalbumin in their milk. J Anim Sci 80:1090–1096.  https://doi.org/10.2527/2002.8041090x CrossRefPubMedPubMedCentralGoogle Scholar
  86. Nottle MB, Nagashima H, Verma PJ, Du ZT, Grupen CG et al (1999) Production and analysis of transgenic pigs containing a metallothionein porcine growth hormon gene construct. In: Murray JD, Anderson GB, Oberbauer AM, McGloughlin MM (eds) Trans-genic animals in agriculture. CABI Publishing, New York, NY, pp 145–156Google Scholar
  87. Palmiter RD, Brinster RL, Hammer RE, Trumbauer ME, Rosenfeld MG, Birnberg NC, Evans RM (1982) Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature 300:611–615PubMedPubMedCentralCrossRefGoogle Scholar
  88. Parc AL, Karav S, Rouquié C, Maga EA, Bunyatratchata A, Barile D (2017) Characterization of recombinant human lactoferrin N-glycans expressed in the milk of transgenic cows. PLoS One 12(2):e0171477.  https://doi.org/10.1371/journal.pone.0171477 CrossRefPubMedPubMedCentralGoogle Scholar
  89. Pinkert CA, Murray JD (1999) Transgenic farm animals. In: Murray JD, Anderson GB, Oberbauer AM, McGloughlin MM (eds) Transgenic animals in agriculture. CAB International, Wallingham, pp 1–18Google Scholar
  90. Pinkert CA, Pursel VG, Miller KF, Palmiter RD, Brinster RL (1987) Production of transgenic pigs harboring growth hormone (MTbGH) or growth hormone releasing factor (MThGRF) genes. J Anim Sci 65(Suppl. 1):260 (Abstr.)Google Scholar
  91. Polge EJC, Barton SC, Surani MAH, Miller JR, Wagner T, Rottman R et al (1989) Induced expression of a bovine growth hormone construct in transgenic pigs: biotechnology of growth regulation. Butterworths, London, pp 279–289Google Scholar
  92. Pursel VG, Rexroad CE Jr (1993) Status of research with transgenic farm animals. J Anim Sci 71(Suppl):10–19PubMedCrossRefPubMedCentralGoogle Scholar
  93. Pursel VG, Rexroad CE Jr, Bolt DJ, Miller KF, Wall RJ, Hammer RE et al (1987) Progress on gene transfer in farm animals. Vet Immunol Immunopathol 17:303–312PubMedCrossRefPubMedCentralGoogle Scholar
  94. Pursel VG, Pinkert CA, Miller KF, Bolt DJ, Campbell RG, Palmiter RD, Brinster RL, Hammer RE (1989) Genetic engineering of livestock. Science 244:1281–1288PubMedCrossRefPubMedCentralGoogle Scholar
  95. Pursel VG, Wall RJ, Solomon MB, Bolt DJ, Murray JD, Ward KA (1997) Transfer of an ovine metallothionein-ovine growth hormone fusion gene into swine. J Anim Sci 75:2208–2214PubMedCrossRefPubMedCentralGoogle Scholar
  96. Pursel V, Wall RJ, Mitchell AD, Elsasser TH, Solomon MB, Coleman ME et al (1999) Expression of insulin-like growth factor I in skeletal muscle of transgenic swine. In: Murray JD, Anderson GB, Oberbauer AM, McGloughlin MM (eds) Transgenic animals in agriculture. CAB International, WallingfordGoogle Scholar
  97. Pursel VG, Mitchell AD, Bee G, Elsasser TH, McMurtry JP, Wall RJ et al (2004) Growth and tissue accretion rates of swine expressing an insulin-like growth factor I transgene. Anim Biotechnol 15:33–45PubMedCrossRefPubMedCentralGoogle Scholar
  98. Reh WA, Maga EA, Collette NMB, Moyer A, Conrad-Brink JS, Taylor SJ, DePeters EJ, Oppenheim S, Rowe JD, BonDurant RH, Anderson GB, Murray JD (2004) Hot topic: using a Stearoyl-CoA Desaturase transgene to Alter milk fatty acid composition. J Dairy Sci 87:3510–3514PubMedCrossRefPubMedCentralGoogle Scholar
  99. Rexroad CE Jr, Hammer RE, Bolt DJ, Mayo KE, Frohman LA, Palmiter RD et al (1989) Production of transgenic sheep with growth-regulating genes. Mol Reprod Dev 1:164–169PubMedCrossRefPubMedCentralGoogle Scholar
  100. Rexroad CE Jr, Mayo K, Bolt DJ, Elsasser TH, Miller KF, Behringer RR et al (1991) Transferrin- and albumin-directed expression of growth-related peptides in transgenic sheep. J Anim Sci 69:2995–3004PubMedCrossRefPubMedCentralGoogle Scholar
  101. Richt JA, Kasinathan P, Hamir AN, Castilla J, Sathiyaseelan T, Vargas F, Sathiyaseelan J, Wu H, Matsushita H, Koster J, Kato S, Ishida I, Soto C, Robl JM, Kuroiwa Y (2007) Production of cattle lacking prion protein. Nat Biotechnol 25:132–138PubMedCrossRefGoogle Scholar
  102. Rocheleau CE, Downs WD, Lin R, Wittmann C, Bei Y, Cha Y-H, Ali M, Priess JR, Mello CC (1997) Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. Cell 90:707–716PubMedCrossRefGoogle Scholar
  103. Rogers GE (1990) Improvement of wool production through genetic engineering. Trends Biotechnol 8:6PubMedCrossRefGoogle Scholar
  104. 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 Δ12 fatty acid desaturase gene from spinach in transgenic pigs. PNAS 101:6361–6366PubMedCrossRefGoogle Scholar
  105. Scharfen EC, Mills DA, Maga EA (2007) Use of human lysozyme transgenic goat milk in cheese making: effects on lactic acid bacteria performance. J Dairy Sci 90:4084–4091PubMedCrossRefPubMedCentralGoogle Scholar
  106. Schnieke AE, Kind AJ, Ritchie WA, Mycock K, Scott AR, Ritchie M, Wilmut I, Colman A, Campbell KHS (1997) Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 278:2130–2133PubMedCrossRefPubMedCentralGoogle Scholar
  107. Shi Y, Berg JM (1995) A direct comparison of the properties of natural and designed zinc-finger proteins. Chem Biol 2:83–89PubMedCrossRefPubMedCentralGoogle Scholar
  108. Simojoki H, Hyvönen P, Orro T, Pyörälä S (2010) High concentration of human lactoferrin in milk of rhLf-transgenic cows relieves signs of bovine experimental Staphylococcus chromogenes intramammary infection. Vet Immunol Immunopathol 136:265–271PubMedCrossRefPubMedCentralGoogle Scholar
  109. Tan W, Carlson DF, Walton MW, Fahrenkrug SC, Hackett PB (2012) Precision editing of large animal genomes. Adv Genet 80:37–97PubMedPubMedCentralGoogle Scholar
  110. Tessanne K, Golding MC, Long CR, Peoples MD, Hannon G, Westhusin ME (2012) Production of transgenic calves expressing an shRNA targeting myostatin. Mol Reprod Dev 79:176–185PubMedCrossRefPubMedCentralGoogle Scholar
  111. Thomassen EA, van Veen HA, van Berkel PH, Nuijens JH, Abrahams JP (2005) The protein structure of recombinant human lactoferrin produced in the milk of transgenic cows closely matches the structure of human milk-derived lactoferrin. Transgenic Res 14:397–405PubMedCrossRefPubMedCentralGoogle Scholar
  112. Tong J, Wei H, Liu X, Hu W, Bi M, Wang YY, Li QY, Li N (2011) Production of recombinant human lysozyme in the milk of transgenic pigs. Transgenic Res 20:417–419PubMedCrossRefPubMedCentralGoogle Scholar
  113. Van Eenennaam AL, Young AE (2014) Prevalence and impacts of genetically engineered feedstuffs on livestock populations1. J Anim Sci 92:4255–4278.  https://doi.org/10.2527/jas.2014-8124 CrossRefPubMedPubMedCentralGoogle Scholar
  114. Vize PD, Michalska AE, Ashman R, Lloyd B, Stone BA, Quinn P et al (1988) Introduction of a porcine growth hormone fusion gene into transgenic pigs promotes growth. J Cell Sci 90:295–300PubMedPubMedCentralGoogle Scholar
  115. Wall RJ, Pursel VG, Hammer RE, Brinster RL (1985) Development of porcine ova that were centrifuged to permit visualization of pronuclei and nuclei. Biol Reprod 32:645–651PubMedCrossRefPubMedCentralGoogle Scholar
  116. Wall RJ, Hawk HW, Nel N (1992) Making transgenic livestock: genetic engineering on a large scale. J Cell Biochem 49:113–120PubMedCrossRefPubMedCentralGoogle Scholar
  117. Wang J, Yang P, Tang B, Sun X, Zhang R, Guo C, Gong G, Liu Y, Li R, Zhang L, Dai Y, Li N (2008) Expression and characterization of bioactive recombinant human alpha-lactalbumin in the milk of transgenic cloned cows. J Dairy Sci 91:4466–4476PubMedCrossRefPubMedCentralGoogle Scholar
  118. Wang YS, He X, Du Y, Su J, Gao M, Ma Y, Hua S, Quan F, Liu J, Zhang Y (2015) Transgenic cattle produced by nuclear transfer of fetal fibroblasts carrying Ipr1 gene at a specific locus. Theriogenology 84:608–616PubMedCrossRefPubMedCentralGoogle Scholar
  119. Ward KA, Nancarrow CD (1991) The genetic engineering of production traits in domestic animals. Experientia 47:913PubMedCrossRefPubMedCentralGoogle Scholar
  120. Ward KA, Franklin IR, Murray JD, Nancarrow CD, Raphael KA, Rigby NW, Byrne CR, Wilson BW, Hunt CL (1986) The direct transfer of DNA by embryo microinjection. Proc. 3rd World Congress Genetics Applied to Livestock Breeding 12:6–21. Lincoln, Nebraska.Google Scholar
  121. Ward KA, Nancarrow CD, Murray JD, Shanahan CM, Byrne CR, Rigby NW, Townrow CA, Leish Z, Wilson BW, Graham NM, Wynn PC, Hunt CL, Speck PA (1990) The current status of genetic engineering in domestic animals. J Dairy Sci 73:2586–2592CrossRefGoogle Scholar
  122. Wheeler MB, Bleck GT, Donovan SM (2001) Transgenic alteration of sow milk to improve piglet growth and health. Reprod Suppl 58:313–324PubMedPubMedCentralGoogle Scholar
  123. Whyte JJ, Zhao J, Wells KD, Samuel MS, Whitworth KM, Walters EM, Laughlin MH, Prather RS (2011) Gene targeting with zinc finger nucleases to produce cloned eGFP knockout pigs. Mol Reprod Dev 78:2PubMedPubMedCentralCrossRefGoogle Scholar
  124. Wiedenheft B, Sternberg SH, Doudna JA (2012) RNA-guided genetic silencing systems in bacteria and archaea. Nature 482:331–338PubMedCrossRefPubMedCentralGoogle Scholar
  125. Wieghart M, Hoover JL, McGrane MM, Hanson RW, Rottman FM, Holtzman SH et al (1990) Production of transgenic pigs harbouring a rat phosphoenolpyruvate carboxykinase-bovine growth hormone fusion gene. J Reprod Fertil Suppl 41:89–96PubMedPubMedCentralGoogle Scholar
  126. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385:810–813PubMedCrossRefPubMedCentralGoogle Scholar
  127. Wu X, Ouyang H, Duan B et al (2012) Production of cloned transgenic cow expressing omega-3 fatty acids. Transgenic Res 21:537–543.  https://doi.org/10.1007/s11248-011-9554-2 CrossRefPubMedPubMedCentralGoogle Scholar
  128. Yang P, Wang J, Gong G, Sun X, Zhang R, Du Z, Liu Y, Li R, Ding F, Tang B, Dai Y, Li N (2008) Cattle mammary bioreactor generated by a novel procedure of transgenic cloning for large-scale production of functional human lactoferrin. PLoS One 3:e3453PubMedPubMedCentralCrossRefGoogle Scholar
  129. Yang B, Wang J, Tang B, Liu Y, Guo C, Yang P, Yu T, Li R, Zhao J, Zhang L, Dai Y, Li N (2011) Characterization of bioactive recombinant human lysozyme expressed in milk of cloned transgenic cattle. PLoS One 6:e17593PubMedPubMedCentralCrossRefGoogle Scholar
  130. Zhang J, Li L, Cai Y, Xu X, Chen J, Wu Y, Yu H, Yu G, Liu S, Zhang A, Chen J, Cheng G (2008) Expression of active recombinant human lactoferrin in the milk of transgenic goats. Protein Expr Purif 57:127–135PubMedCrossRefPubMedCentralGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Animal ScienceUniversity of CaliforniaDavisUSA
  2. 2.Department of Population Health and ReproductionUniversity of CaliforniaDavisUSA

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