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Retinoblastoma in transgenic mice

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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.

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Authors and Affiliations

  1. Regulatory Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California, 92037, USA

    Jolene J. Windle & Pamela L. Mellon

  2. Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles Street, Boston, Massachusetts, 02114, USA

    Daniel M. Albert, Joan M. O'Brien & Dennis M. Marcus

  3. Department of Pathology, University of Washington, School of Medicine, Seattle, Washington, 98195, USA

    Christine M. Disteche

  4. Massachusetts General Hospital Cancer Center, Harvard Medical School, Bldg. 149 13th Street, Charlestown, Massachusetts, 02129, USA

    Rene Bernards

Authors
  1. Jolene J. Windle
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  2. Daniel M. Albert
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  3. Joan M. O'Brien
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  4. Dennis M. Marcus
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  5. Christine M. Disteche
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  6. Rene Bernards
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  7. Pamela L. Mellon
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Windle, J., Albert, D., O'Brien, J. et al. Retinoblastoma in transgenic mice. Nature 343, 665–669 (1990). https://doi.org/10.1038/343665a0

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

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