Somatic cell hybridization is a technique recently used for bringing genomes of two cells together in a single nucleus. It has proved to be a valuable tool for the study of human gene linkage and control of differentiation in cultured animal cells. Complementation analysis in somatic cell hybrids of a number of diseases has led to a better understanding of the inheritance and the pathogenesis of hereditary diseases. In order for this techniqe to be further aplied to problems in medicine, it is necessary to develop new selective systems for retaining particular human chromosomes in human-muscle hybrids. Any abnormal genes on the human chromosomes can then be studied with biochemical methods. This research proposal concerns the development of two selective systems using adenosine kinase and adenosine deaminase as selective markers. Mouse cell mutants lacking these enzymes will be isolated and fused with human cells. These human-mouse hybrids will then be used for gene linkage analyses. Besides genetic experiments, the adenosine deaminase-deficient mutant could be a model system for the study of an immunodeficiency disease associated with a deficiency in this enzyme. I will also study, by using the mouse mutant lacking deoxycytidin deaminase, the mechanism of gene transfer mediated by Herpes simplex virus. Herpes viruses have been associated with many chronic diseases; cytomegalovirus with mental retardation and the Epstein-Barr virus with a cancer. Through an understanding of Herpes simplex virus-medited gene transfer, the mechanism of a unique host- virus relationship in these diseases could be elucidated. An adequate collection of selective markers may reveal somatic crossing over events hitherto unobserved in mammalian somatic cells. If this is found, somatic cell hybridization with gene recombination could be a basis for developing a new approach to "gene therapy" of hereditary diseases.