Found in Wild Mice

~Glucuronidase (Gus) has been extensively studied in the mouse as a model of mammalian gene regulation. The structural gene maps to chromosome 5 and variation for the regulation of Gus gene expression co segregates with the structural locus. The regulatory phenotypes include variation in systemic levels of gene expression (Pfister et al., 1985), variation in testosterone induction of kidney B-glucuroni­ dase (Palmer et al.,1983; Swank et al., 1973) and variation in Gus expression within individual organs. The various structural and regula­ tory phenotypes which cosegregate at the GUS locus are designated as haplotypes [Gus] and the different regulatory phenotypes have been designated as separate elements of the haplotype complex (Table 1) (Paigen, 1979). Three haplotypes of structural and regulatory alleles of GUS have been characterized among inbred strains (Pfister et al., 1982). These combinations of alleles of enzyme structure and regulation are present in all laboratory strains and they have not been separated by recom­ bination either in backcrosses of up to 1000 mice (Swank et al., 1978) or in the construction of congenic and recombinant inbred (RI) strains. More recently, the analysis of genomic DNA restriction patterns using a cDNA probe has revealed that these allelic haplotypes differ at at least three positions along the gene as shown by altered fragment sizes in Southern blot analysis (Elliott et al., 1985). In this instance, the [Gus]H and [Gus]B haplotypes do not differ from each other but they both differ from [Gus]A at all three positions (Table 2). We have sampled diverse house mouse species for variation in 1) gene structure, 2) gene expression at the level of processing and turnover, and 3) gene regulation at the level of systemic synthesis and in the response of the kidney Gus locus to testosterone. We specifically asked whether there was-CVidence of independent variation for enzyme structure and regulation of synthesis. We have identified six new alleles of enzyme structure, three new variants of GUS regulation and seven new haplotypes. These provide important new insights into the regulation of GUS expression which might not have been readily determined from a molecular analysis of the GUS genomic structures found among inbred strains.