Genetic and molecular characterization of glucuronidase structure and function has provided an important model system for gene regulation in eukaryotes. Glucuronidase is androgen induced in kidney proximal tubule cells. Genetic variation in androgen induction is observed among inbred strains. This variation segregates as a single gene determining rate of enzyme synthesis that is closely linked with the glucuronidase structural gene Gus. Three surveys of wild mice have recently uncovered five additional combinations. We propose to use wild mouse populations to study the genetic regulation of glucuronidase in several important ways: first, as a source of new structural and regulatory variants; second, as an independent test of whether structural and regulatory properties are independent or altered by single mutational events; third, as a source of recombination events between regulatory and structural sites. The various combinations of structural and regulatory genes are being characterized for structural changes in the glucuronidase molecule and for kinetic parameters defining the induction of enzyme synthesis. A broad sampling of the mouse gene pool will provide a more accurate assessment of the variation of glucuronidase regulation. Additionally, the new variants will expend our ability to analyze the molecular function of regulatory sequences. The wild derived resources will also be characterized at the level of mRNA and genomic DNA in the accompanying proposal by Kenneth Paigen. This may provide an important means of fine structural mapping of glucuronidase and its associated regulatory sites in the mouse genome and allow correlations of structure and function in a mammalian regulatory gene.