History of Genetic Engineering of Laboratory and Farm Animals

  • Caird E. RexroadJr.
Part of the Basic Life Sciences book series


In the last few hundred years, man has learned that the tools of ge netic selection are a powerful means of improving the utility of livestock. Genetic engineering of animals appears to be a logical extension of the man-animal relationship; albeit one that places more responsibility on man in his efforts to develop an ecosystem in which both man and animals persist. The prospects for genetic engineering of farm animals have improved dramatically because of recent discoveries in the field of gene regulation. Two fundamental tools have made possible the recently reported successful insertion of a cloned human growth hormone gene into pigs and sheep (21). These tools or biotechnologies are embryo micromanipulation and recombinant DNA technology. Judicious application of embryo manipulation and recombinant DNA will provide an opportunity to increase the utilization of animals for food, fiber, and biomedical products. Combining genetic manipulation with the well-established biotechnologies of semen and embryo preservation has increased man’s options for preserving genetic resources that at present seem to be dwindling through the loss of animal species in a technology-dominated world. In this chapter, I will discuss methods of genetic manipulation developed since 1950 that appear to have made the most impact on efforts to genetically engineer farm animals. I will also discuss the potential and problems that have arisen with different approaches to engineering animals. The development of recombinant DNA techniques is outside the scope of this chapter, but is obviously an essential part of genetic engineering.


Thymidine Kinase Nuclear Transfer Nuclear Transplantation Thymidine Kinase Gene Mouse Blastocyst 
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  1. 1.
    Bradley, A., M. Evans, M.H. Kaufman, and E. Robertson (1984) Formation of germ line chimaeras from embryo-derived teratocarcinoma cell lines. Nature 309:255–256.PubMedCrossRefGoogle Scholar
  2. 2.
    Brem, G., H. Tenhumberg, and H. Kraublich (1984) Chimerism in cattle through microsurgical aggregation of morulae. Theriogenology 22:609.PubMedCrossRefGoogle Scholar
  3. 3.
    Briggs, R., and T.J. King (1952) Transplantation of living nuclei from blastula cells into enucleated frogs’ eggs. Proc. Natl. Acad. Sci., USA 38:455–457.PubMedCrossRefGoogle Scholar
  4. 4.
    Brinster, R.L. (1974) The effect of cells transferred into the mouse blastocyst on subsequent development. J. Exptl. Med. 140:1049–1056.CrossRefGoogle Scholar
  5. 5.
    Brinster, R.L., H.Y. Chen, M.E. Trumbauer, M.K. Yagle, A.W. Senear, R. Warren, and R.D. Palmiter (1981) Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs. Cell 27:223–231.PubMedCrossRefGoogle Scholar
  6. 6.
    Butler, J.E., G.B. Anderson, R.H. BonDurant, and R.L. Pashen (1985) Production of ovine chimeras. Theriogenology 23:183.CrossRefGoogle Scholar
  7. 7.
    Colman, A. (1975) Transcription of DNA’s of known sequence after injection into the eggs and oocytes of Xenopus laevis. Eur. J. Biochem.57:85–96.PubMedCrossRefGoogle Scholar
  8. 8.
    Constantini, F., and E. Lacy (1981) Introduction of a rabbit ß-globin gene in the mouse germ line. Nature 294:92–94.CrossRefGoogle Scholar
  9. 9.
    Evans, M.J., and M.H. Kaufman (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156.PubMedCrossRefGoogle Scholar
  10. 10.
    Fehilly, C.B., S.M. Willadsen, and E.M. Tucker (1984) Experimental chimerism in sheep. J. Reprod. Fert. 70:347–351.CrossRefGoogle Scholar
  11. 11.
    Fehilly, C.B., S.M. Willadsen, and E.M. Tucker (1984) Interspecific chimerism between sheep and goats. Nature 307:634–636.PubMedCrossRefGoogle Scholar
  12. 12.
    Fischberg, M., J.B. Gurdon, and J.R. Elsdale (1958) Nuclear transplantation in Xenopus laevis. Nature 181:424.CrossRefGoogle Scholar
  13. 13.
    Frels, W.I., J.A. Bluestone, R.J. Hodes, M.R. Capecchi, and D.S. Singer (1985) Expression of a microinjected porcine class I major histocompatibility complex gene in transgenic mice. Science 228:577–580.PubMedCrossRefGoogle Scholar
  14. 14.
    Gardner, R.L. (1968) Mouse chimeras obtained by injection of cells into the blastocyst. Nature 220:596–597.PubMedCrossRefGoogle Scholar
  15. 15.
    Goldberg, D.A., J.W. Posakony, and T. Maniatis (1983) Correct developmental expression of a cloned alcohol dehydrogenase gene transduced into the Drosophila germ line. Cell 34:59–73.PubMedCrossRefGoogle Scholar
  16. 16.
    Gordon, J.W., and F.H. Ruddle (1981) Integration and stable germ line transmission of genes injected into mouse pronuclei. Science 214: 1244–1246.PubMedCrossRefGoogle Scholar
  17. 17.
    Gordon, J.W., G.A. Scangos, D.J. Plotkin, J.A. Barbosa, and F.H. Ruddle (1980) Genetic transformation of mouse embryos by microinjec tion of purified DNA. Proc. Natl. Acad. Sci., USA 77:7380–7384.PubMedCrossRefGoogle Scholar
  18. 18.
    Graham, F.L., and A.J. Van Dereb (1973) A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52:456–467.PubMedCrossRefGoogle Scholar
  19. 19.
    Gurdon, J.B. (1962) Adult frogs derived from the nuclei of single somatic cells. Biology 4:256–273.Google Scholar
  20. 20.
    Gurdon, J.B., and R.A. Laskey (1970) The transplantation of single nuclei from single cultured cells into enucleate frogs’ eggs. J. Embr. and Exptl. Morph. 24:227–248.Google Scholar
  21. 21.
    Hammer, R.E., V.G. Pursel, C.E. Rexroad, R.J. Wall, D.J. Bolt, K.M. Ebert, R.D. Palmiter, and R.L. Brinster (1985) Production of transgenic rabbits, sheep and pigs by microinjection. Nature 315:680–683.PubMedCrossRefGoogle Scholar
  22. 22.
    Harbers, K., D. Jahner, and R. Jaenish (1981) Microinjection of cloned retroviral genomes into mouse zygotes: Integration and expression in the animal. Nature 293:540–542.PubMedCrossRefGoogle Scholar
  23. 23.
    Illmensee, K., and P.C. Hoppe (1981) Nuclear transplantation in Mus musculus: Developmental potential of nuclei from preimplantation embryos. Cell 23:9–18.PubMedCrossRefGoogle Scholar
  24. 24.
    Jaenisch, R. (1976) Germ line integration and Mendelian transmission of exogenous Moloney leukemia virus. Proc. Natl. Acad. Sci., USA73:1260–1264.PubMedCrossRefGoogle Scholar
  25. 25.
    Jaenisch, R., K. Harbers, A. Schnieke, J. Lohler, I. Chumakov, D. Jahner, D. Grotkopp, and E. Hoffman (1983) Germline integration of Moloney Murine Leukemia virus at the Mov-13 locus leads to recessive lethal mutation and early embryonic death. Cell 32:209–216.PubMedCrossRefGoogle Scholar
  26. 26.
    Jaenisch, R., and B. Mintz (1974) Simian Virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA. Proc. Natl. Acad. Sci., USA 71:1250–1254.PubMedCrossRefGoogle Scholar
  27. 27.
    Jahner, D., and R. Jaenisch (1980) Integration of Moloney leukemia virus into the germ line of mice: Correlation between site of integration and virus activation. Nature 287:456–458.PubMedCrossRefGoogle Scholar
  28. 28.
    King, T.J., and R. Briggs (1955) Changes in the nuclei of differentiating gastrula cells as demonstrated by nuclear transplantation. Proc. Natl. Acad. Sci., USA 41:321–325.PubMedCrossRefGoogle Scholar
  29. 29.
    McGrath, J., and D. Solter (1983) Nuclear transplantation in the mouse embryo by microsurgery and cell fusion. Science 220:1300–1302.PubMedCrossRefGoogle Scholar
  30. 30.
    McGrath, J., and D. Solter (1984) Inability of mouse blastomere nuclei transferred to enucleated zygotes to support development in vitro. Science 226:1317–1319.PubMedCrossRefGoogle Scholar
  31. 31.
    Mertz, J.E., and J.B. Gurdon (1977) Purified DNAs are transcribed after microinjection into Xenopus oocytes. Proc. Natl. Acad. Sci., USA 74:1502–1506.PubMedCrossRefGoogle Scholar
  32. 32.
    Miller, A.D., E.S. Ong, M.G. Rosenfeld, I.M. Verma, and R.M. Evans (1984) Infectious and selectable retrovirus containing an inducible rat growth hormone minigene. Science 225:993–998.PubMedCrossRefGoogle Scholar
  33. 33.
    Mintz, B. (1962) Formation of genetically mosaic mouse embryos. Am. Zool. 2:432.Google Scholar
  34. 34.
    Mintz, B. (1971) Allophenic mice of multi-embryo origin. In Methods in Mammalian Embryology, J. Daniel, ed. W.H. Freeman, San Francisco, pp. 186–214.Google Scholar
  35. 35.
    Mintz, B., and K. Illmensee (1975) Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc. Natl. Acad. Sci., USA 72:3585–3589.PubMedCrossRefGoogle Scholar
  36. 36.
    O’Hare, K., and G.M. Rubin (1983) Structures of P transposable elements and their sites of insertion and excision in the Drosophila melanogaster genome. Cell 34:25–35.PubMedCrossRefGoogle Scholar
  37. 37.
    Ornitz, D.M., R.D. Palmiter, R.E. Hammer, R.L. Brinster, G.H. Swift, and R.J. MacDonald (1985) Specific expression of an elastase-human growth hormone fusion gene in pancreatic acinar cells of transgenic mice. Nature 313:600–602.PubMedCrossRefGoogle Scholar
  38. 38.
    Palmiter, R.D., R.L. Brinster, R.E. Hammer, M.E. Trumbauer, M.G. Rosenfeld, N.C. Birnberg, and R.M. Evans (1982) Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature 300:611–615.PubMedCrossRefGoogle Scholar
  39. 39.
    Palmiter, R.D., T.M. Wilkie, H.Y. Chen, and R.L. Brinster (1984) Transmission distortion and mosaicism in an unusual transgenic mouse pedigree. Cell 36:869–877.PubMedCrossRefGoogle Scholar
  40. 40.
    Papaioannou, V.E., M.W. McBurney, R.L. Gardener, and M.J. Evans (1975) Fate of teratocarcinoma cells injected into early mouse embryos. Nature 258:70–73.PubMedCrossRefGoogle Scholar
  41. 41.
    Paulson, K.E., N. Deka, C.W. Schmid, R. Misra, C.W. Schindler, M.G. Rush, L. Kadyk, and L. Leinwald (1985) A transposon-like element in human DNA. Nature 316:359–361.PubMedCrossRefGoogle Scholar
  42. 42.
    Pighills, E., J.L. Hancock, and J.G. Hall (1968) Attempted induction of chimerism in sheep. J. Reprod. Fert. 17:543–547.CrossRefGoogle Scholar
  43. 43.
    Rossant, J., and W.I. Frels (1980) Interspecific chimeras in mammals: Successful production of live chimeras between Mus musculus and Mus carol. Science 208:419–421.PubMedCrossRefGoogle Scholar
  44. 44.
    Rubin, G., and A.C. Spralding (1982) Genetic transformation of Droso-phila with transposable element vectors. Science 218:348–353.PubMedCrossRefGoogle Scholar
  45. 45.
    Rusconi, S., and W. Schaffner (1981) Transformation of frog embryos with a rabbit ß-globin gene. Proc. Natl. Acad. Sci., USA 78:5051–5055.PubMedCrossRefGoogle Scholar
  46. 46.
    Scangos, G., and F.H. Ruddle (1981) Mechanisms and applications of DNA-mediated gene transfer in mammalian cells-A review. Gene 14: 1–10.PubMedCrossRefGoogle Scholar
  47. 47.
    Schnieke, A., K. Harbers, and R. Jaenisch (1983) Embryonic lethal mu tation in mice induced by retrovirus insertion in the -l(I) collagen gene. Nature 304:315–320.PubMedCrossRefGoogle Scholar
  48. 48.
    Scholnick, S.B., B.A. Morgan, and J. Hirsh (1983) The cloned Dopa decarboxylase gene is developmentally regulated when reintegrated into the Drosophila genome. Cell 34:37–45.PubMedCrossRefGoogle Scholar
  49. 49.
    Shani, M. (1985) Tissue-specific expression of rat myosin light-chain 2 gene in transgenic mice. Nature 314:283–286.PubMedCrossRefGoogle Scholar
  50. 50.
    Smith, L.D. (1965) Transplantation of nuclei of primordial germ cells into enucleated eggs of Rana pipiens. Proc. Natl. Acad. Sci., USA54:101–107.PubMedCrossRefGoogle Scholar
  51. 51.
    Spralding, A.C., and G. Rubin (1982) Transposition of cloned P elements into Drosophila germ line chromosomes. Science 218:341–347.CrossRefGoogle Scholar
  52. 52.
    Stevens, L.C. (1970) The development of transplantable teratocarcinomas from intratesticular grafts of pre-and postimplantation embryos. Dev. Biol. 21:364–382.PubMedCrossRefGoogle Scholar
  53. 53.
    Stewart, C.L., H. Stuhlmann, D. Jahner, and R. Jaenisch (1982) De novo methylation, expression, and infectivity of retroviral genomes introduced into embryonal carcinoma cells. Proc. Natl. Acad. Sci., USA79:4098–4102.PubMedCrossRefGoogle Scholar
  54. 54.
    Tarkowski, A.K. (1961) Mouse chimaeras developed from fused eggs. Nature 190:857–860.PubMedCrossRefGoogle Scholar
  55. 55.
    Tucker, E.M., R.M. Moor, and L.E.A. Rowson (1974) Tetraparental sheep chimeras induced by blastomere transplantation: Changes in blood type with age. Immunology 26:613–621.PubMedGoogle Scholar
  56. 56.
    Wagner, E.F., T.A. Stewart, and B. Mintz (1981) The human ß-globin gene and a functional viral thymidine kinase gene in developing mice. Proc. Natl. Acad. Sci., USA 78:5016–5020.PubMedCrossRefGoogle Scholar
  57. 57.
    Wagner, E.F., L. Covarrubias, T.A. Stewart, and B. Mintz (1984) Prenatal lethalities in mice homozygous for human growth hormone gene sequences integrated into the germ line. Cell 35:647–655.CrossRefGoogle Scholar
  58. 58.
    Wagner, T.E., P.C. Hoppe, J.D. Jollick, D.R. Scholl, R.L. Hodinka, and J.B. Gault (1981) Microinjection of a rabbit ß-globin gene into zy gotes and its subsequent expression in adult mice and their offspring. Proc. Natl. Acad. Sci., USA 78:6376–6380.PubMedCrossRefGoogle Scholar
  59. 59.
    Wall, R.J., V.G. Pursel, R.E. Hammer, and R.L. Brinster (1985) Development of porcine ova that were centrifuged to permit visualization of pronuclei and nuclei. Biol. Reprod. 32:645–651.PubMedCrossRefGoogle Scholar
  60. 60.
    Wigler, M., S. Silverstein, L.S. Lee, A. Pellicer, Y.C. Cheng, and R. Axel (1977) Transfer of purified herpes simplex virus thymidine kinase genes to cultured mouse cells. Cell 11:223–232.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Caird E. RexroadJr.
    • 1
  1. 1.ARS, Reproduction LaboratoryU.S. Department of AgricultureBeltsvilleUSA

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