Histidine decarboxylase phenotypes of inbred mouse strains: a regulatory locus (Hdc) determines kidney enzyme concentration.

Mouse kidney histidine decarboxylase (HDC) provides a model system to study genetic control of a hormone-regulated enzyme (inducible by estrogen and thyroxine; repressible by testosterone). Five major HDC phenotypes scored on the basis of (i) enzyme activity and (ii) the difference in activity between the sexes (females usually higher than males) have been discovered by screening 38 strains of mice. One genetic difference between high-activity strains (DBA/2 and C3H/He) and low-activity strains (C57BL/6 and C57BL/10) has been examined in detail. The phenotypic difference segregates as a single gene in both conventional crosses and between recombinant inbred (RI) strains. Immunoprecipitation has shown that the activity difference is due to an alteration in the number of enzyme molecules. The phenotypic difference between high and low strains can therefore be attributed to different alleles of a single regulatory locus, Hdc; the allele Hdcb determines low HDC concentration, and the allele Hdcd high concentration. Hdc has been mapped to chromosome 2 using data from both comparisons of strain distribution patterns of previously mapped loci within RI strains and a conventional three-point cross. The probable gene order is B2m-pa-Hdc, with map distances of 3.1 +/- 1.7 and 2.0 +/- 1.4 cM, respectively.