Transgenic mice harboring SV40 t-antigen genes develop characteristic brain tumors |
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Authors: | Ralph L. Brinster Howard Y. Chen Albee Messing Terry van Dyke Arnold J. Levine Richard D. Palmiter |
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Affiliation: | 1. Laboratory of Reproductive Physiology School of Veterinary Medicine University of Pennsylvania Philadelphia, Pennsylvania 19104 USA;2. Department of Pathology and Laboratory Medicine School of Medicine University of Pennsylvania Philadelphia, Pennsylvania 19104 USA;3. Department of Microbiology State University of New York Stony Brook, New York 11794 USA;4. Howard Hughes Medical Institute Department of Biochemistry University of Washington Seattle, Washington 98195 USA |
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Abstract: | A high percentage of transgenic mice developing from eggs microinjected with plasmids containing the SV40 early region genes and a metallothionein fusion gene develop tumors within the choroid plexus. A line of mice has been established in which nearly every affected animal succumbs to this brain tumor. Thymic hypertrophy and kidney pathology are also observed in some mice. SV40 T-antigen mRNA and protein are readily detected in affected tissues; however, SV40 T-antigen gene expression is barely detectable in unaffected tissues or in susceptible tissues prior to overt pathology, suggesting that tumorigenesis depends upon activation of the SV40 genes. Comparison of DNA from tumor tissue (or cell lines derived from tumors) with DNA from unaffected tissues reveals structural rearrangements as well as changes in DNA methylation of the foreign DNA. The SV40 genes are frequently amplified in tumor tissue, which further indicates that their expression is intimately involved in tumorigenesis in transgenic mice. |
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