We have been successful in the last few years in introducing new genes into the germ line of mice. A significant number of these new genes have been expressed in the animals and their progeny. The present study involves the introduction of onc genes into mice. Many of the studies will be done with the SV40 early region which contains the large T and small t antigen genes. We have found this region will induce choroid plexus adenomas and carcinomas in transgenic mice. The genes are also expressed in other tissues of the animal. This provides a novel and exciting model in which to study the mechanism of oncogenesis. We wish to investigate the: (1) events associated with activation of the gene (e.g., DNA methylation, amplification, rearrangement); (2) role of the large T and small t coding sequences in tumor development; (3) role of enhancer elements in the frequency and target cell specificity of tumor development; (4) effects of other onc genes, such as src and ras; and (5) effect of carcinogenic agents on transgenic mice that contain onc genes but do not show obvious signs of malignancy. The ability to introduce known oncogenic DNA sequences into an animal and study the effect of the genes provides an excellent experimental system for studying cancer. The experiments in animals are particularly important for the identification of DNA changes associated in vivo with gene activation and factors controlling tissue-specific expression. (X)
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