Two experimental protocols will be employed to examine the role of gene enhancer signals in regulating gene expression of viruses in a tissue restricted fashion. 1. Transgenic mice with SV40 DNA in all cells and the germ line have been obtained. With several independently derived mice of this type there is a tissue restricted or preferred gene expression of SV40 mRNA and tumor antigen (brain, thymus, kidney). Similarly there is a tissue limited or preferred SV40 induced tumorigenesis in these transgenic mice. Experiments have been designed to determine which genetic elements of SV40 DNA (gene enhancer, T-antigen, t-antigen) are responsible for tissue limited gene expression and/or tumorigenesis in these transgenic mice. Transgenic mice containing viral "immortality" gene functions of polyoma, adenovirus and SV40 will be obtained and the role of these gene products in tumorigenesis will be studied. Permanent cell lines derived from a variety of tissues of these transgenic mice can be useful to study developmental questions or detect possible oncogenes. 2. The role of the polyoma gene enhancer sequences in regulating gene expression in embryonal carcinoma cells and a variety of differentiated cell types will be studied. Several methods for obtaining gene enhancer mutants with a cell or tissue preference are described. Such gene enhancer mutants should be useful in experiments with transgenic mice.