The Gene Mutated in Bare Patches and Striated Mice Encodes a Novel 3beta-hydroxysteroid Dehydrogenase

Nat Genet. 1999 Jun;22(2):182-7. doi: 10.1038/9700.

Abstract

X-linked dominant disorders that are exclusively lethal prenatally in hemizygous males have been described in human and mouse. None of the genes responsible has been isolated in either species. The bare patches (Bpa) and striated (Str) mouse mutations were originally identified in female offspring of X-irradiated males. Subsequently, additional independent alleles were described. We have previously mapped these X-linked dominant, male-lethal mutations to an overlapping region of 600 kb that is homologous to human Xq28 (ref. 4) and identified several candidate genes in this interval. Here we report mutations in one of these genes, Nsdhl, encoding an NAD(P)H steroid dehydrogenase-like protein, in two independent Bpa and three independent Str alleles. Quantitative analysis of sterols from tissues of affected Bpa mice support a role for Nsdhl in cholesterol biosynthesis. Our results demonstrate that Bpa and Str are allelic mutations and identify the first mammalian locus associated with an X-linked dominant, male-lethal phenotype. They also expand the spectrum of phenotypes associated with abnormalities of cholesterol metabolism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / chemistry
  • 3-Hydroxysteroid Dehydrogenases / genetics*
  • Alleles
  • Amino Acid Sequence
  • Animals
  • Chromosome Mapping
  • Crosses, Genetic
  • Exons
  • Eye Abnormalities / enzymology
  • Eye Abnormalities / genetics
  • Female
  • Fibroblasts / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutation*
  • Point Mutation
  • Sequence Alignment
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Sex Chromosome Aberrations*
  • Skin / metabolism
  • Skin Abnormalities / enzymology
  • Skin Abnormalities / genetics
  • X Chromosome*

Substances

  • 3-Hydroxysteroid Dehydrogenases
  • Nsdhl protein, mouse

Associated data

  • GENBANK/AF100198