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.

  • Letter
  • Published:

Retinoblastoma in transgenic mice

Abstract

RETINOBLASTOMA, a malignancy of the eye occurring in young children, has been widely studied as a model for genetic predisposition to cancer. This disease is caused by mutations in both alleles of an anti-oncogene (the reti no blastema gene, Rb) that inactivate or eliminate the Rb encoded protein, p105Rb(refs 1 and 2). Here we report that expression of a viral oncogene, the simian virus 40 T antigen, in the retina of transgenic mice produces heritable ocular tumours with histological, ultrastructural and immunohis-tochemical features identical to those of human retinoblastoma. Furthermore, we demonstrate a specific association3 between pl05Rb and T antigen in mouse retinoblastoma tumour cells. Thus, the occurrence of these tumours is in vivo evidence for oncogenesis due to the ocular-specific expression of an Rb-binding oncoprotein that can functionally inactivate the Rb protein. As an animal model for heritable retinoblastoma, these mice should allow the study of the ontogeny, pathogenesis and treatment of this malignant disease.

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

Access options

Buy this article

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

Similar content being viewed by others

References

  1. Friend, S. H. et al. Nature 323, 643–646 (1986).

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Lee, W.-H. et al. Science 235, 1394–1399 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  3. DeCaprio, J. A. et al. Cell 54, 275–283 (1988).

    Article  CAS  PubMed  Google Scholar 

  4. Talmadge, K., Vamvakopoulos, N. C. & Fiddes, J. C. Nature 307, 37–40 (1984).

    Article  ADS  CAS  PubMed  Google Scholar 

  5. Brinster, R. L. et al. Cell 37, 367–379 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jenkins, N. A. & Copeland, N. G. in Important Advances in Oncology (eds DeVita, V. T., Hellum, S. & Rosenberg, S. A.) 61–77 (Lippincott, Philadelphia, 1989).

    Google Scholar 

  7. Hanahan, D. Nature 315, 115–122 (1985).

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Mahon, K. A. et al. Science 235, 1622–1628 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  9. Baetge, E. E., Behringer, R. R., Messing, A., Brinster, R. L. & Palmiter, R. D. Proc. natn. Acad. Sci. U.S.A. 85, 3648–3652 (1988).

    Article  ADS  CAS  Google Scholar 

  10. Botteri, F. M., van der Putten, H., Wong, D. F., Sauvage, C. A. & Evans, R. M. Molec. cell. Biol. 7, 3178–3184 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ts'o, M. O. M., Zimmerman, L. E. & Fine, B. S. Am. J. Ophthal. 69, 339–349 (1970).

    Article  CAS  PubMed  Google Scholar 

  12. Ts'o, M. O. M., Fine, B. S. & Zimmerman, L. E. Am. J. Ophthal. 69, 350–359 (1970).

    Article  CAS  PubMed  Google Scholar 

  13. Albert, D. M., Sang, D. N. & Craft, J. L. Jap. J. Ophthal. 22, 358–374 (1978).

    Google Scholar 

  14. Flexner, S. Bull. Johns Hopkins Hosp. 2, 115–119 (1891).

    Google Scholar 

  15. Wintersteiner, H. Das Neuroepithelioma Retinae: Eine Anatomische und Klinische Studie (Franz Deuticke, Vienna, 1887).

    Google Scholar 

  16. Wright, J. H. J. exp. Med. 12, 556 (1910).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kyritsis, A. P., Tsokos, M., Triche, T. J. & Chader, G. J. Nature 307, 471–473 (1984).

    Article  ADS  CAS  PubMed  Google Scholar 

  18. Kivela, T. Antigenic Properties of Retinoblastoma Tissue in Relation to Neuronal and Glial Cells of the Human Retina 51–67 (University of Helsinki, 1987).

    Google Scholar 

  19. Stone, J. C. et al. Genomics 5, 70–75 (1989).

    Article  CAS  PubMed  Google Scholar 

  20. Hsieh, C.-L. et al. Somatic Cell molec. Genet. 15, 461–464 (1989).

    Article  CAS  Google Scholar 

  21. Whyte, P. et al. Nature 334, 124–129 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  22. Dyson, N., Howley, P. M., Munger, K. & Harlow, E. Science 243, 934–936 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  23. Ludlow, J. W. et al. Cell 56, 57–65 (1989).

    Article  CAS  PubMed  Google Scholar 

  24. Green, M. R. Cell 56, 1–3 (1989).

    Article  CAS  PubMed  Google Scholar 

  25. Bernards, R. et al. Proc. natn. Acad. Sci. U.S.A. 86, 6474–6478 (1989).

    Article  ADS  CAS  Google Scholar 

  26. Harlow, E. et al. J. Virol. 39, 861–869 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Lane, D. P. & Crawford, L. V. Nature 278, 261–263 (1979).

    Article  ADS  CAS  PubMed  Google Scholar 

  28. Sarnow, P., Yo, Y., Williams, J. & Levine, A. J. Cell 28, 387–394 (1982).

    Article  CAS  PubMed  Google Scholar 

  29. Efrat, S., Baekkeskov, S., Lane, D. & Hanahan, D. EMBO J. 6, 2699–2704 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Chirgwin, J. M., Przybyla, A. E., MacDonald, R. J. & Rutter, W. J. Biochemistry 18, 5294–5299 (1979).

    Article  CAS  PubMed  Google Scholar 

  31. Mellon, P. L., Parker, V., Gluzman, Y. & Maniatis, T. Cell 27, 279–288 (1981).

    Article  CAS  PubMed  Google Scholar 

  32. Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1982).

    Google Scholar 

  33. Tooze, J. (ed.) Molecular Biology of Tumor Viruses. Part 2 (Cold Spring Harbor Laboratory, New York, 1981).

  34. Hogan, B., Costantini, F. & Lacy, E. Manipulating the Mouse Embryo: A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1986).

    Google Scholar 

  35. Tedder, T. F. et al. J. Immun. 141, 4388–4394 (1988).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Windle, J., Albert, D., O'Brien, J. et al. Retinoblastoma in transgenic mice. Nature 343, 665–669 (1990). https://doi.org/10.1038/343665a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/343665a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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