Xy. Liu et al., The gene mutated in bare patches and striated mice encodes a novel 3 beta-hydroxysteroid dehydrogenase, NAT GENET, 22(2), 1999, pp. 182-187
X-linked dominant disorders that are exclusively lethal prenatally in hemiz
ygous males have been described in human and (1). None of the genes respons
ible has been isolated in mouse either species; The bare patches (Bpa):and
striated (Str) mouse mutations were originally identified in female offspri
ng of X-irradiated males(2) (3). Subsequently, additional independent allel
es were described. We have previously mapped these X-linked dominant, male-
lethal mutations to an overlapping region:of 600 kb that is homologous to h
uman Xq28 (ref. 4) and identified several candidate genes in this: interval
(5). 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 i
ndependent Str alleles. Quantitative analysis of sterols from tissues of af
fected Bpa mice support a role for Nsdhl in cholesterol biosynthesis. Our r
esults demonstrate that Bpa and Sfr are allelic mutations and identify the
first mammalian locus associated with an X-linked dominant, male-lethal phe
notype. They also expand the spectrum of phenotypes associated with abnorma
lities of cholesterol metabolism.