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Generation Of Transgenic Dairy Cattle Using ‘in vitro’ Embryo Production

Bio/Technology volume 9, pages 844–847 (1991)Cite this article

Abstract

We have combined gene transfer, by microinjection, with ‘in vitro’ embryo production technology, enabling us to carry out non-surgical transfer, to recipient cows, of microinjected embryos that have been cultured from immature oocytes. Using this approach, we have established 21 pregnancies from which 19 calves were born. Southern blot analysis proved that in two cases the microinjected DNA had been integrated in the host genome.

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References

  1. Gordon, K., Lee, E., Vitale, J.A., Smith, A.E., Westphal, H. and Hennighausen, L. 1987. Production of human tissue plasminogen activator in transgenic mouse milk. Bio/Technology 5: 1183–1187.

    CAS  Google Scholar 

  2. Pittius, C.W., Hennighausen, L., Lee, E., Westphal, H., Nicols, E., Vitale, J. and Gordon, K. 1988. A milk protein gene promoter directs expression of human tissue plasminogen activator cDNA to the mammary gland in the transgenic mice. Proc. Natl. Acad. Sci. USA 85: 5874–5878.

    Article  CAS  Google Scholar 

  3. Archibald, A.L., McClenaghan, M., Hornsey, V., Simons, J.P. and Clark, A.J. 1990. High-level expression of biologically active human α1-antitrypsin in the milk of transgenic mice. Proc. Natl. Acad. Sci. USA 87: 5178–5182.

    Article  CAS  Google Scholar 

  4. Simons, J., McClenaghan, M. and Clark, A. 1987. Alteration of the quality of milk by expression of β-lactoglobulin in transgenic mice. Nature 328: 530–532.

    Article  CAS  Google Scholar 

  5. Meade, H., Gates, L., Lacy, E. and Lonberg, N. 1990. Bovine αS1-casein gene sequences direct high level expression of active human urokinase in mouse milk. Bio/Technology 8: 443–446.

    CAS  PubMed  Google Scholar 

  6. Buehler, T., Bruyere, T., Went, D., Stranzinger, G. and Buerki, K. 1990. Rabbit β-casein promoter directs secretion of human interleukin-2 into the milk of transgenic rabbits. Bio/Technology 8: 140–143.

    CAS  Google Scholar 

  7. Simons, J.P., Wilmut, I., Clark, A.J., Archibald, A.L., Bishop, J.O. and Lathe, R. 1988. Gene transfer into sheep. Bio/Technology 6: 179–183.

    CAS  Google Scholar 

  8. Hammer, R.E., Pursel, V., Rexroad, C., Wall, R., Bolt, D., Ebert, K., Palmiter, R. and Brinster, R. 1985. Production of transgenic rabbits, sheep and pigs by microinjection. Nature 315: 680–683.

    Article  CAS  Google Scholar 

  9. Brem, G., Brenig, B., Goodman, H., Selden, R., Graf, F., Kruff, B., Springman, K., Hondele, J., Meyer, J., Winnacker, E. and Kraublich, H. 1985. Production of transgenic rabbits and pigs. Zuchthygiene 20: 251–252.

    Article  Google Scholar 

  10. Clark, A., Bessos, H., Bishop, J., Brown, P., Harris, S., Lathe, R., McClenaghan, M., Prowse, C., Simons, J., Whitehaw, C. and Wilmut, I. 1989. Expression of human anti-hemophilic factor IX in the milk of transgenic sheep. Bio/Technology 7: 487–492.

    CAS  Google Scholar 

  11. Wall, R.J., Pursel, V.G., Shamay, A., McKnight, R.A., Pittius, C.W. and Hennighausen, L. 1991. High-level synthesis of a heterologous milk protein in the mammary gland of transgenic swine. Proc. Natl. Acad. Sci. USA 88: 1696–1700.

    Article  CAS  Google Scholar 

  12. Swaisgood, H.E. 1982. In: Developments in Dairy Chemistry-1, p. 1–59. P. P. Fox (Ed.). Elsevier Applied Science Publisher, London.

    Google Scholar 

  13. Parrish, J., Susko-Parrish, J., Leibfried-Rutledge, M., Critser, E., Eyestone, W. and First, N. 1986. Bovine in vitro fertilization with frozen-thawed semen. Theriogenology 25: 591–600.

    Article  CAS  Google Scholar 

  14. Wall, R., Pursel, V., Hammer, R. and Brinster, R. 1985. Development of porcine ova that were centrifuged to permit visualization of pronuclei and nuclei. Biol. Reprod. 32: 645–651.

    Article  CAS  Google Scholar 

  15. Hogan, B., Costantini, F. and Lacy, E. 1986. Manipulating the Mouse Embryo: A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.

    Google Scholar 

  16. Eyestone, W., Jones, J. and First, N. 1991. Some factors affecting the efficacy of conditioned medium for the culture of early bovine embryos. J. Reprod. Fert. 92: 59–64.

    Article  CAS  Google Scholar 

  17. Linder, G.M. and Wright, R.W., Jr. 1983. Bovine embryo morphology and evaluation. Theriogenology 20: 407–416.

    Article  Google Scholar 

  18. Massey, J. and Oden, A. 1984. No seasonal effect on embryo donor performance in the south west region of the USA. Theriogenology 21: 196–217.

    Article  Google Scholar 

  19. Markette, K., Seidel, G., Jr. and Elsden, R. 1985. Estimation of embryonic losses in bovine embryo transfer recipients from progesteron profiles and returns to estrus. Theriogenology 23: 45–62.

    Article  CAS  Google Scholar 

  20. Rey, M.W., Woloshuk, S.L., de Boer, H.A. and Pieper, F.R. 1990. Complete nucleotide sequence of human mammary gland lactoferrin. Nucl. Acids Res. 18: 5288.

    Article  CAS  Google Scholar 

  21. Huang, M.T.F. and Gorman, C.M. 1990. Intervening sequences increase efficiency of RNA 3′ processing and accumulation of cytoplasmic RNA. Nucl. Acids Res. 18: 937–947.

    Article  CAS  Google Scholar 

  22. Palmiter, R.D., Sandgren, E.P., Avarbock, M.R., Allen, D.D. and Brinster, R.L. 1991. Heterologous introns can enhance expression of transgenes in mice. Proc. Natl. Acad. Sci. USA 88: 478–482.

    Article  CAS  Google Scholar 

  23. Blom van Assendelft, G. 1989. Dominant control region of the human β-like globin cluster, p. 65–66. Ph.D. thesis, University of Groningen, The Netherlands.

    Google Scholar 

  24. Biery, K.A., Bondioli, K.R. and DeMayo, F.J. 1988. Gene transfer by pronuclear injection in the bovine. Theriogenology 29: 224 (abstr.).

    Article  Google Scholar 

  25. Massey, J. 1990. Animal production industry in the year 2000 A.D. J. Reprod. Fert., Suppl. 41: 199–208.

    CAS  Google Scholar 

  26. Bracket, B., Oh, Y., Evans, J. and Donawick, W. 1980. Fertilization and early development of cow ova. Biol. Reprod. 23: 189–205.

    Article  Google Scholar 

  27. Eyestone, W., Leibfried-Rutledge, M., Northey, D., Gilligan, B. and First, N. 1987. Culture of one- and two-cell bovine embryos to the blastocyst stage in the ovine oviduct. Theriogenology 28: 1–7.

    Article  CAS  Google Scholar 

  28. Boland, M. 1984. The use of the rabbit oviduct as a screening tool for the viability of mammalian eggs. Theriogenology 21: 126–137.

    Article  Google Scholar 

  29. Pieterse, M., Vos, P., Kruip, T., Willemse, A. and Taverne, M. 1991. Characteristics, of bovine cycles during repeated transvaginal, ultrasound-guided puncturing of follicles for ovum pick-up. Theriogenology 35: 399–412.

    Article  Google Scholar 

  30. Van der Schans, A., Van der Westerlaken, L., De Wit, A., Eyestone, W. and de Boer, H. 1991. Ultrasound-guided transvaginal collection of oocytes in the cow. Theriogenology 35: 288 (abstr.).

    Article  Google Scholar 

  31. Bavister, B., Leibfried, M. and Lieberman, G. 1983. Development of preimplantation embryos of the golden hamster in a defined medium. Biol. Reprod. 28: 235–247.

    Article  CAS  Google Scholar 

  32. Sambrook, J., Fritsch, E.F. and Maniatis, T. 1989. Molecular Cloning, a Laboratory Manual. Second edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.

    Google Scholar 

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Author notes

  1. Herman de Boer: Corresponding author.

Authors and Affiliations

  1. Department of Embryology, Gene Pharming Europe B.V., Niels Bohrweg 11–13, 2333 CA, Leiden, The Netherlands

    Paul Krimpenfort & Adriana Rademakers

  2. Department of Biochemistry, University of Leiden, The Netherlands

    Will Eyestone & Herman de Boer

  3. Research Institute for Animal Production, PO Box 501, 3700 AM, Zeist, The Netherlands

    Adriaan van der Schans

  4. Department of Molecular Biology, Gene Pharming Europe B.V., Niels Bohrweg 11–13, 2333 CA, Leiden, The Netherlands

    Sandra van den Broek, Patricia Kooiman, Erika Kootwijk, Gerard Platenburg, Frank Pieper, Rein Strijker & Herman de Boer

Authors
  1. Paul Krimpenfort
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  2. Adriana Rademakers
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  3. Will Eyestone
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  4. Adriaan van der Schans
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  5. Sandra van den Broek
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  6. Patricia Kooiman
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  7. Erika Kootwijk
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  8. Gerard Platenburg
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  9. Frank Pieper
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  10. Rein Strijker
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  11. Herman de Boer
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Krimpenfort, P., Rademakers, A., Eyestone, W. et al. Generation Of Transgenic Dairy Cattle Using ‘in vitro’ Embryo Production. Nat Biotechnol 9, 844–847 (1991). https://doi.org/10.1038/nbt0991-844

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  • DOI: https://doi.org/10.1038/nbt0991-844

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