The Genes Encoding Gonadal and Nongonadal Forms of 3[beta]-Hydroxysteroid Dehydrogenase/[Delta]5-[Delta]4 Isomerase Are Closely Linked on Mouse Chromosome 3

Abstract

The biosynthesis of steroid hormones in the gonads and adrenal glands requires the activities of the enzyme 3[beta]-hydroxysteroid dehydrogenase/isomerase (3[beta]HSD) which catalyzes the NAD+-dependent dehydrogenation and subsequent [Delta]5 --> [Delta]4 isomerization of [Delta]5-3[beta]-hydroxysteroids to [Delta]4-3-ketosteroids. The mouse expresses four isoforms of 3[beta]HSD. 3[beta]HSD I is expressed in gonads and adrenal glands and appears to be the major steroidogenic form, 3[beta]HSDs II and III are expressed in both liver and kidneys, and 3[beta]HSD IV has been detected only in kidneys. To determine the genetic relationship between the 3[beta]HSD isoforms, we have mapped the chromosomal locations of the four genes by linkage analysis using gene-specific probes derived from the 3' untranslated regions of 3[beta]HSD cDNA clones. The four 3[beta]HSD structural genes (Hsd3b) are closely linked within a segment of chromosome 3 that is conserved on human chromosome 1. The order of markers on Chr 3 surrounding Hsd3b is: centromere-Gba-(4.4 +/- 2.2)-Hsd3b-(3.3 +/- 1.9)-Tshb-(6.7 +/- 2.7)-Amy-1.