Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter

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Publication Type Journal Article
School or College School of Medicine
Department Ophthalmology
Creator Baehr, Wolfgang
Other Author al-Ubaidi, M. R.; Font, R. L.; Quiambao, A. B.; Keener, M. J.; Liou, G. I.; Overbeek, P A
Title Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter
Date 1992
Description We have previously shown that postnatal expression of the viral oncoprotein SV40 T antigen in rod photoreceptors (transgene MOT1), at a time when retinal cells have withdrawn from the mitotic cycle, leads to photoreceptor cell death (Al-Ubaidi et al., 1992. Proc. Natl. Acad. Sci. USA. 89:1194-1198). To study the effect of the specificity of the promoter, we replaced the mouse opsin promoter in MOT1 by a 1.3-kb promoter fragment of the human IRBP gene which is expressed in both rod and cone photoreceptors during embryonic development. The resulting construct, termed HIT1, was injected into mouse embryos and five transgenic mice lines were established. Mice heterozygous for HIT1 exhibited early bilateral retinal and brain tumors with varying degrees of incidence. Histopathological examination of the brain and eyes of three of the families showed typical primitive neuroectodermal tumors. In some of the bilateral retinal tumors, peculiar rosettes were observed, which were different from the Flexner-Wintersteiner rosettes typically associated with human retinoblastomas. The ocular and cerebral tumors, however, contained Homer-Wright rosettes, and showed varying degrees of immunoreactivity to antibodies against the neuronal specific antigens, synaptophysin and Leu7, but not to antibodies against photoreceptor specific proteins. Taken together, the results indicate that the specificity of the promoter used for T antigen and/or the time of onset of transgene expression determines the fate of photoreceptor cells expressing T antigen.
Type Text
Publisher Rockefeller University Press
Volume 119
Issue 6
First Page 1681
Last Page 1687
Subject Simian virus 40; Retinol-Binding Proteins; Promoter Regions (Genetics)
Subject MESH Antigens, Viral, Tumor; Eye Proteins; Gene Expression Regulation, Neoplastic
Language eng
Bibliographic Citation al-Ubaidi MR, Font RL, Quiambao AB, Keener MJ, Liou GI, Overbeek PA, Baehr W. (1992). Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter. J Cell Biol, 119(6), 1681-7
Rights Management (c) Rockefeller University Press
Format Medium application/pdf
Identifier ir-main,1717
ARK ark:/87278/s6cz3rtk
Setname ir_uspace
Date Created 2012-06-13
Date Modified 2012-06-13
ID 707483
Reference URL https://collections.lib.utah.edu/ark:/87278/s6cz3rtk
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