Nature Genetics
22, 182 - 187 (1999)
doi:10.1038/9700
The gene mutated in bare patches and striated mice encodes a novel 3 -hydroxysteroid
dehydrogenaseXiao Yu Liu1, 7, Andrew W. Dangel1, 7, Richard I. Kelley2, Wei Zhao1, Paul Denny3, Marc Botcherby4, Bruce Cattanach3, Jo Peters3, Patricia R. Hunsicker5, Ann-Marie Mallon3, Mark A. Strivens3, Rachael Bate3, Webb Miller6, Michael Rhodes4, Stephen D.M. Brown3
& Gail E. Herman11
Children's Hospital Research Foundation and Department
of Pediatrics, The Ohio State University, Columbus,
Ohio 43205, USA. 2
The Kennedy Krieger Institute and Department of Pediatrics,
John Hopkins University, Baltimore, Maryland
21205, USA. 3
MRC Mouse Genome Centre and Mammalian Genetics Unit
, Harwell, OX11 ORD, UK. 4
MRC Human Genome Mapping Project Resource Centre,
Hinxton, Cambridge, UK. 5
Life Sciences Division, Oak Ridge National Laboratory
, Oak Ridge, Tennessee 37831, USA
. 6
Department of Computer Science, The Pennsylvania State
University, University Park, Pennsylvania 16802,
USA. 7
These authors contributed equally to this work.
Correspondence should be addressed to Gail E. Herman hermang@pediatrics.ohio-state.eduX-linked dominant disorders that are exclusively lethal prenatally in hemizygous
males have been described in human and mouse1. 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 males2,
3. 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 interval5. 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.
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