DIRECTED EXPRESSION OF SIMIAN-VIRUS-40 T-ANTIGEN IN TRANSGENIC MICE USING THE EPIDERMAL GROWTH-FACTOR GENE PROMOTER

A transgenic mouse line (EGF/Tag) has been established in which expres sion of SV40 T-antigen is directed by a 5.5 kb fragment of the 5'-flan king region of the mouse epidermal growth factor (EGF) gene. Of the tw o principal sites of EGF expression in mice, submaxillary gland and ki dney, T-antigen mRNA and protein were detected in the former but not i n the latter tissue of the EGF/Tag animals. T-antigen expression in th e submaxillary gland was restricted to the EGF-producing cells of the granular convoluted tubules, and the oncoprotein induced hyperplasia o f these cells. T-antigen levels were markedly higher in the submaxilla ry glands of male compared with female transgenic mice, suggesting tha t expression of the transgene was androgen-regulated, like the endogen ous EGF gene. These results indicate that the 5.5 kb fragment upstream of the mouse EGF gene contains the DNA enhancer elements required for hormonally regulated expression in the submaxillary gland. Since the hyperplastic submaxillary glands of the EGF/Tag mice continue to synth esize EGF, these glands provide a tissue source from which it may prov e possible to establish EGF-secreting cell lines for further in vitro studies of the mechanisms regulating expression of the EGF gene.