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Rescuing Transgene Expression by Co-Integration

Bio/Technology volume 10, pages 1450–1454 (1992)Cite this article

Abstract

To test whether foreign gene expression can be improved in transgenic mice by manipulating the site of integration, we co-integrated the efficiently expressed sheep β-lactoglobulin gene with two poorly expressed β-lactoglobulin-derived genes encoding human proteins. In each case, we observed a significant improvement in the frequency and level of expression of the hybrid gene. “Rescuing” transgene expression by co-integration may provide a general solution for improving the efficiency of heterologous gene expression in transgenic animals.

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References

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

    Article  CAS  PubMed  Google Scholar 

  2. Harris, S., McClenaghan, M., Simons, J.P., Ali, S. and Clark, A.J. 1991. Developmental regulation of the sheep β-lactoglobulin gene in transgenic mice. Devel. Genet. 12: 299–307.

    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 transgenic mice. Proc. Natl. Acad. Sci. USA 87: 5178–5182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wright, G., Carver, A., Cottom, D., Reeves, A., Scott, A., Simons, P., Wilmut, I., Garner, I. and Colman, A. 1991. High level expression of active human α-1-antitrypsin in the milk of transgenic sheep. Bio/Technology 9: 830–834.

    CAS  Google Scholar 

  5. Whitelaw, C.B.A., Archibald, A.L., Harris, S., McClenaghan, M., Simons, J.P. and Clark, A.J. 1991. Targeting expression to the mammary gland; intronic sequences can enhance the efficiency of gene expression in transgenic mice. Transgenic Res. 1 3–13.

    Article  CAS  PubMed  Google Scholar 

  6. Brinster, R.L., Allen, J.M., Behringer, R.R., Gelinas, R.E. and Palmiter, R.D. 1988. Introns increase transcriptional efficiency in transgenic mice. Proc. Natl. Acad. Sci. USA 85: 836–840.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Palmiter, R.D., Sandgren, E.P., Avarbock, M.R., Allen, J.M. and Brinster, R.L. 1991. Heterologous introns can increase expression in transgenic mice. Proc. Natl. Acad. Sci. USA 88: 478–482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Allen, N.D., Cran, D.G., Barton, S.G., Hettle, S., Reik, W. and Surani, M.A. 1988. Trangenes as probes for active chromosomal domains in mouse development. Nature 333: 852–855.

    Article  CAS  PubMed  Google Scholar 

  9. Al-Shawi, R., Kinnaird, J., Burke, J. and Bishop, J.O. 1990. Expression of a foreign gene in a line of transgenic mice is modulated by a chromosomal position effect. Mol. Cell. Biol. 10: 1192–1198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bonnerot, C., Grimber, G., Briand, P. and Nicolas, J.-F. 1990. Patterns of expression of position dependent integrated transgenes in mouse embryos. Proc. Natl. Acad. Sci. USA 87: 6331–6335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Storb, U., Pinkert, C., Arp, B., Engler, P., Gollahon, K., Manz, J., Brady, W. and Brinster, R.L. 1986. Transgenic mice with mu and kappa genes encoding antiphosphorylcholine. J. Exp. Med. 164: 627–641.

    Article  CAS  PubMed  Google Scholar 

  12. Behringer, R.R., Ryan, T.M., Reilly, M.P., Asakura, T., Palmiter, R.D. and Brinster, R.L., 1989. Synthesis of functional hemoglobin in transgenic mice. Science 245: 971–973.

    Article  CAS  PubMed  Google Scholar 

  13. Whitelaw, C.B.A., Harris, S., McClenaghan, M., Simons, J.P. and Clark, A.J. 1992. Position-independent expression of the ovine β-lactoglobulin gene in transgenic mice. Biochem. J. 286 31–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  15. Kellum, R. and Schedl, P. 1991. A position effect assay for boundaries of higher order chromosomal domains. Cell 64: 941–950.

    Article  CAS  PubMed  Google Scholar 

  16. Ali, S. and Clark, A.J. 1988. Characterisation of the gene encoding ovine β-lactoglobulin. J. Mol. Biol. 199: 415–426.

    Article  CAS  PubMed  Google Scholar 

  17. Ali, S., McClenaghan, M., Simons, J.P. and Clark, A.J. 1990. Characterisation of the alleles encoding ovine β-lactoglobulins A and B. Gene 91: 201–207.

    Article  CAS  PubMed  Google Scholar 

  18. Clark, A.J., Bessos, H., Bishop, J.O., Brown, P., Harris, S., Lathe, R., McClenaghan, 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 

  19. Ciliberto, G., Dente, L. and Cortese, R. 1985. Cell-specific expression of a transfected α1-antirypsin gene. Cell 41: 531–540.

    Article  CAS  PubMed  Google Scholar 

  20. Anson, D.S., Austen, D.E.G. and Brownlee, G.G. 1985. Expression of active human clotting factor IX from recombinant DNA clones in mammalian cells. Nature 315: 683–685.

    Article  CAS  PubMed  Google Scholar 

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Author notes

  1. A. J. Clark: Corresponding author.

Authors and Affiliations

  1. AFRC Institute of Animal Physiology and Genetics Research, Edinburgh Research Station, Roslin, Midlothian, EH25 9PS, Scotland

    A. J. Clark, A. Cowper, R. Wallace & J. P. Simons

  2. Pharmaceutical Proteins Ltd, Centre for Genome Research, King's Buildings, West Mains Road, Edinburgh, EH9 3JQ, Scotland

    G. Wright

Authors
  1. A. J. Clark
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  2. A. Cowper
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  3. R. Wallace
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  4. G. Wright
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  5. J. P. Simons
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Clark, A., Cowper, A., Wallace, R. et al. Rescuing Transgene Expression by Co-Integration. Nat Biotechnol 10, 1450–1454 (1992). https://doi.org/10.1038/nbt1192-1450

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  • DOI: https://doi.org/10.1038/nbt1192-1450

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