The Ephx1 ^d allele encoding an Arg338Cys substitution is associated with heat lability

Abstract.

Heat lability of the mouse hepatic microsomal epoxide hydrolase 1 enzyme-specific activity (EC 3.3.2.3) is greater for the A/J than the C57BL/6J strain. Analysis of the microsomal epoxide hydrolase 1 cDNA coding sequences shows the C57BL/6J and A/J strains to differ in a single base, a C to T transition at position 1012 from the ATG. This change would predict a substitution of an Arg for a Cys at codon 338. Lyman et al. (J. Biol. Chem 255:8650, 1980) studied 26 inbred mouse strains and assigned each strain to one of two groups based upon functional criteria that included heat lability and pH optima for microsomal epoxide hydrolase 1. The heat-labile strains including A/J were denoted with the Ephx1 ^d allele, whereas C57BL/6J and other members of the heat-stable strains were denoted with the Ephx1 ^b allele. We examined those same inbred mouse strains and found complete concordance between the assignment of microsomal epoxide hydrolase 1 allele superscript ``b'' or ``d'' and the wild-type and C1012T polymorphism respectively (Fisher's Exact Test, two-sided p < 0.0001). These data suggest that mouse hepatic microsomal epoxide hydrolase 1 heat lability is associated with the presence of a Cys at residue 338. Genomic samples from the available AXB and BXA recombinant inbred strains were allelotyped for the SNP identified in the Ephx1 gene that distinguishes the A/J and C57BL/6J parental strains and used to map Ephx1 to Chromosome (Chr) 1 at approximately 98.5cM (LOD = 10.0).