Retinoblastoma in transgenic mice

Jolene J. Windle, Daniel M. Albert, Joan M. O'Brien, Dennis M. Marcus, Christine M. Disteche, Rene Bernards, Pamela L. Mellon

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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.

Original languageEnglish (US)
Pages (from-to)665-669
Number of pages5
JournalNature
Volume343
Issue number6259
DOIs
StatePublished - 1990

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    Windle, J. J., Albert, D. M., O'Brien, J. M., Marcus, D. M., Disteche, C. M., Bernards, R., & Mellon, P. L. (1990). Retinoblastoma in transgenic mice. Nature, 343(6259), 665-669. https://doi.org/10.1038/343665a0