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American Journal of Pathology, Vol 135, 401-410, Copyright © 1989 by American Society for Investigative Pathology

REGULAR ARTICLES

Metal-inducible pathology in the liver, pancreas, and kidney of transgenic mice expressing SV40 early region genes

KR Dyer and A Messing
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison 53706.

Transgenic mice (SV-202) that carry the SV40 early region genes under the control of an inverted metallothionein promoter developed islet cell adenomas, hepatocellular carcinomas, and a generalized peripheral neuropathy. Both the islet cell adenomas and the hepatocellular carcinomas developed from the proliferation of T antigen-positive cells. However, T antigen expression was not seen in either the peripheral or central nervous systems. Stimulation of the metallothionein promoter with heavy metals altered the temporal onset of hepatic expression and broadened the distribution of oncogene expression to include exocrine pancreas and renal tubular epithelium. Although solid tumors were not seen in the exocrine pancreas or kidneys of SV-202 mice, all immunopositive tissues developed histologic changes. These results indicate that metallothionein-directed T antigen expression can induce abnormal cellular growth in a variety of tissues, and the distribution of these tissues can be manipulated with heavy metals.


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M. J. Haas, Y. P. Dragan, H. Hikita, R. Shimel, K. Takimoto, S. Heath, J. Vaughan, and H. C. Pitot
Transgene Expression and Repression in Transgenic Rats Bearing the Phosphoenolpyruvate Carboxykinase-Simian Virus 40 T Antigen or the Phosphoenolpyruvate Carboxykinase-Transforming Growth Factor-{alpha} Constructs
Am. J. Pathol., July 1, 1999; 155(1): 183 - 192.
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Copyright © 1989 by the American Society for Investigative Pathology.