Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Paper
  • Published:

Rabbit β-Casein Promoter Directs Secretion of Human Interleukin-2 into the Milk of Transgenic Rabbits

Bio/Technology volume 8, pages 140–143 (1990)Cite this article

Abstract

To test the potential usefulness of transgenic rabbits as production systems for human proteins of pharmaceutical value, we cloned the rabbit β-casein promoter and fused it to the genomic sequence of the human interleukin-2 (hIL2) gene. Four transgenic female rabbits were tested for expression and biological activity of the foreign protein in their milk. The milk of all four females proved to contain biologically active hIL2. The results show that transgenic rabbits may represent a convenient and economic system for the rapid production of biologically active protein in milk.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

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 plajminogen activator cDNA to the mammary gland in the transgenic mice. Proc. Natl. Acad. Sci. USA 85: 5874–5878.

    Article  CAS  Google Scholar 

  3. Clark, A.J., Bessos, H., Bishop, J.O., Brown, P., Harris, S., Lathe, R., McCenaghan, M., Prowse, C., Simons, J.P., Whitelaw, C.B.A. 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 

  4. Simons, J.P., Wilmut, L., 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 

  5. Van Brunt, J. 1988. Molecular farming: Transgenic animals as bio-reactors. Bio/Technology 6: 1149–1154.

    Article  Google Scholar 

  6. Vakulenko, I.S. 1984. Milk yield of rabbits and the growth of their young. Krolikovodstvo i Zverovodstve 5: 11–13.

    Google Scholar 

  7. Cowie, A.T. 1969. Variations in the yield and composition of the milk during lactation in the rabbit and the galactopoietic effect of prolactin. J. Endocr. 44: 437–450.

    Article  CAS  Google Scholar 

  8. Jeness, R. and Sloan, R.E. 1970. The composition of milks of various species—a review. Dairy Sci. Abstr. 32: 599–612.

    Google Scholar 

  9. Dayal, R., Hurlimann, J., Suard, M.L. and Kraehenbuhl, J-P. 1982. Chemical and immunochemical characterization of caseins and the major whey proteins of rabbit milk. Biochem. J. 201: 71–79.

    Article  CAS  Google Scholar 

  10. Bühler, Th.A., Bruyè;re, Th. and Bürki, K. 1989. Nucleotide sequence of the rabbit β-casein 5′ flanking region. EMBL database No. X15735.

    Google Scholar 

  11. Degrave, W., Tavernier, J., Duerink, F., Plaetinck, G., Devos, R. and Fiers, W. 1983. Cloning and structure of the human interleukin-2 chromosomal gene. EMBO J. 2: 2349–2353.

    Article  CAS  Google Scholar 

  12. Smith, K.A., 1988. Interleukin-2: Inception, impact and implications. Science 240: 1169–1176.

    Article  CAS  Google Scholar 

  13. Sanger, F., Nicklen, S. and Coulson, A.R. 1977. DNA sequencing with chain termination inhibitors. Proc. Natl. Acad. Sci. USA 74: 5463–5467.

    Article  CAS  Google Scholar 

  14. Jones, W.K., Yu-Lee, L., Clift, S.M., Brown, T.L. and Rosen, J.M. 1985. The rat casein multigene family. J. Biol. Chem. 260: 7042–7050.

    CAS  PubMed  Google Scholar 

  15. Gorodetsky, S.I., Tkach, T.M. and Kapelinskaya, T.V. 1988. Isolation and characterization of the Bos taurus β-casein gene. Gene 66: 87–96.

    Article  CAS  Google Scholar 

  16. Yu-Lee, L., Richter-Mann, L., Couch, C.H., Stewart, A.F., Mackinlay, A.G. and Rosen, J.M. 1986. Evolution of the casein multigene family: conserved sequences in the 5′ flanking and exon regions. Nucl. Acids Res. 14: 1883–1902.

    Article  CAS  Google Scholar 

  17. Scheidereit, C., Westphal, H., Carlson, C., Bosshard, H. and Beato, M. 1986. Molecular model of the interaction between the glucocorticoid receptor and the regulatory elements of inducible genes. DNA 5: 383–391.

    Article  CAS  Google Scholar 

  18. Brinster, R.L., Chen, H.Y., Trumbauer, M.E., Yagle, M.K. and Palmiter, R.D. 1985. Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs. Proc. Natl. Acad. Sci. U.S.A. 82: 4438–4442.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  20. Robb, R.J., 1982. Human T-cell growth factor: Purification, biochemical characterisation, and interaction with a cellular receptor. Immunobiol. 161: 21–50.

    Article  CAS  Google Scholar 

  21. Lebas, F. 1970. Description d'une machine à traire les lapins. Ann. Zootech. 19: 223–228.

    Article  Google Scholar 

  22. Lee, K.F., Atiee, S.H. and Rosen, J.M. 1989. Differential regulation of rat β-casem-chloraraphenicol acetyltransferase fusion gene expression in transgenic mice. Mol. Cell. Biol. 9: 560–565.

    Article  CAS  Google Scholar 

  23. Bornstein, P., McKay, J., Liska, D.J., Apone, S. and Devarayalu, S. 1988. Interactions between the promoter and the first intron are involved in transcriptional control of α1(I) collagen gene expression. Mol. Cell. Biol. 8: 4851–4857.

    Article  CAS  Google Scholar 

  24. Lee, K.F., DeMayo, F.J., Atiee, S.H. and Rosen, J.M. 1988. Tissue specific expression of the rat β-casein gene in transgenic mice. Nucl. Acids Res. 16: 1027–1041.

    Article  CAS  Google Scholar 

  25. Grosveld, F., van Assendelft, G.B., Greaver, D.R. and Kollias, G. 1987. Position-independent, high-level expression of the human β-globin gene in transgenic mice. Cell 51: 975–985.

    Article  CAS  Google Scholar 

  26. Talbot, D., Collis, P., Antoniou, M., Vidal, M., Grosveld, F. and Greaves, D.R. 1989. A dominant control region from the human β-globin locus conferring integration site-independent gene expression. Nature 338: 352–355.

    Article  CAS  Google Scholar 

  27. Zoller, M.J. and Smith, M. 1983. Oligonucleotide-directed mutagenesis of DNA fragments cloned into M13 vectors. Methods in Enzymol. 100: 468–500.

    Article  CAS  Google Scholar 

  28. Ogden, R.C. and Adams, D.A. 1987. Electrophoresis in agarose and acrylamide gels. Methods in Enzymol. 152: 61–87.

    Article  CAS  Google Scholar 

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

    Google Scholar 

  30. Schreier, M.H. and Tees, R. Long-term culture and cloning of specific helper T cells, p. 263–275. In: Immunological Methods. Vol. 2. Academic Press, N.Y.

    Chapter  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Swiss Federal Institute of Technology Zürich, Institute for Animal Science, CH-8092, Zürich

    Th. A. Bühler, D. F. Went & G. Stranzinger

  2. Preclinical Research, Sandoz Ltd., CH-4002, Basel

    Th. Bruyère & K. Bürki

Authors
  1. Th. A. Bühler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Th. Bruyère
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. F. Went
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Stranzinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Bürki
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bühler, T., Bruyère, T., Went, D. et al. Rabbit β-Casein Promoter Directs Secretion of Human Interleukin-2 into the Milk of Transgenic Rabbits. Nat Biotechnol 8, 140–143 (1990). https://doi.org/10.1038/nbt0290-140

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt0290-140

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing