These transgenic mice express the mouse cyclin D1 under the direction of the rat fatty acid binding protein 1 promoter (&#8211;596 to +21 fragment). Mice that are hemizygous for the transgene are viable, normal in size and do not display any gross physical or behavioral abnormalities. Hemizygous mutant mice exhibit reduced fertility after 3 months of age. Transgenic mice overexpress cyclin D1 in the liver and epithelial cells of the small intestine and colon. A lower level of expression occurs in the kidneys. Onset of progressive liver disease begins at one month of age with hepatomegaly. Male transgenic mice exhibit more severe hepatomegaly than transgenic females. By 6 months of age, all transgenic males and half of the transgenic females display hepatocellular dysplasia. 87% of transgenic males and 69% of transgenic females develop hepatocellular adenoma or hepatocellular carcinoma by 15 months of age. By 6 months of age, approximately half of mutant mice have lost hepatic expression of <i>Smad4</i>. This mutant mouse strain may be useful in studies of hepatocellular carcinogenesis. 

These mice express a transgene containing the mouse cyclin D1 gene that is over-expressed in the liver and epithelial cells of the small intestine and colon.



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