Glucuronidase phenotypes of inbred mouse strains.

M A M M A L I A N ,&glucuronidase has been relatively well characterized with regard to such parameters as substrate specificity, tissue levels, pH dependence, intracellular localization, and protein structure. For a recent review the reader may consult LEVVY and CONCHIE (1966). Although this information failed to elucidate the physiolcigical role of glucuronidase, it has provided a convenient tool for the study of biochemical genetics in mammalian systems. I n one of the earliest reports of a biochemical variant in higher organisms, MORROW, GREENSPAN, and CARROLL (1949, 1950) described two closely related inbred mouse strains (Mus musculus) that showed only one tenth the liver glucuronidase activity of six other lines of inbred mice. Subsequently, from an extensive genetic study, LAW, MORROW, and GREENSPAN (1 952) concluded that a single recessive allele was responsible for this difference. The locus involved is presumed to be the structural gene for glucuronidase since mutants produce a physically altered enzyme (PAIGEN 1961a ) . Genetically it is closely linked to the retinal degeneraation gene (PAIGEN and NOELL 1961) and recently has been identified as part of linkage group XVII ( SIIIMAN and GREEN 1965). The low glucuronidase phenotype is the consequence of both a generalized decrease in enzyme activity and an altered time course of glucuronidase accumulation during post-natal development (PAIGEN 1961 b). The formation of a structurally altered enzyme protein also influences the intracellular localization of the enzyme. In the hepatic cells of normal animals the enzyme is present in approximately equal amounts in the lysosomes and the membranes of the ergastoplasm, while in the structural gene mutant the residual activity is preferentially located in lysosomes. The present study reports an attempt to find additional variants of glucuronidase which might be useful in the analysis of this enzyme in particular and, hopefully, the general problem of gene expression in higher organisms. For this purpose the glucuronidase phenotypes of a large number of inbred strains of the house mouse have been studied. Inbred mice were chosen as the subjects for several reasons: (1 ) a large number of inbred strains of independent origins exist, thus providing the necessary genetic diversity among which variants could be expected to occur; (2) if a new variant is discovered, a genetically uniform stock is immediately available; ( 3 ) mice are large enough 1.0 provide adequate quantities of tissue for biochemical