Amplification of a SV40 T antigen transgene is associated with sarcomagenesis in mice.
Transgenic mice harboring simian virus 40 large T antigen (Tag) gene fused to an erythroid-specific enhancer developed soft tissue sarcomas which expressed very high levels of T antigen. The Tag expression was not detectable in the animals' non-transformed tissues. While mice bearing several copies of the transgene developed tumors at an early age of 4-6 months, those with a single copy had a delayed onset of 10-16 months, and DNA analysis of their tumors showed amplification of the Tag transgene. Amplification of a Tag transgene has also been described previously in brain tumors. Our studies demonstrate that Tag transgene amplification is not restricted to a particular construct or a single tumor type. Therefore, this may be a general mechanism for Tag-mediated carcinogenesis, and our transgenic mouse system can be useful for elucidating the mechanisms that govern the amplification process of Tag sequences in vivo.
Teitz
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Howard Hughes Medical Institute, University of California, San Francisco 94143-0724.
Yen
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D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D015139:Blotting, Southern; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005784:Gene Amplification; D005814:Genes, Viral; D005914:Globins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D012091:Repetitive Sequences, Nucleic Acid; D012513:Sarcoma, Experimental / Q000235:genetics*; D013539:Simian virus 40 / Q000235:genetics / Q000276:immunology; D013997:Time Factors
D000952:Antigens, Polyomavirus Transforming; D004273:DNA, Neoplasm; D005914:Globins