Genetic polymorphism of microsomal epoxide hydrolase activity in the mouse.

Hepatic microsomal epoxide hydrolase activity (EC 3.3.2.3), assayed using styrene oxide as the substrate, has a pH optimum of 9.5 from C57BL/6J mice and a pH optimum of 8.7 from DBA/2J mice. In cross and back-cross matings between C57BL/6J and DBA/2J mice, this phenotypic difference in epoxide hydrolase activity is inherited as a single autosomal trait, with co-dominant expression in heterozygotes. Heating liver microsomes from C57Bl/6J mice at 62 degrees C for 30 min produced a slight decrease in enzyme activity, whereas the same treatment of DBA/2J microsomes reduced enzyme activity to less than 3% of its initial value. Twenty-six inbred strains of mice were examined and separated into two phenotypic classes on the basis of differences in pH optima and heat sensitivity of microsomal epoxide hyrolase activity. Eph-1 is proposed as the locus symbol of the structural gene for microsomal epoxide hydrolase, with superscripts b and d designating the alleles carried by C57BL/6J and DBA/2J mice, respectively. Using 24 recombinant inbred strains derived from C57BL/6J and DBA/2J mice, Eph-1 was found to be linked to two loci on Chromosome 1.