title: The gene mutated in bare patches and striated mice encodes a novel 3beta-hydroxysteroid dehydrogenase.
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.
authors.affiliation: Children's Hospital Research Foundation and Department of Pediatrics, The Ohio State University, Columbus 43205, USA.
authors.forename: X Y
authors.initials: XY
authors.lastname: Liu
authors.forename: A W
authors.initials: AW
authors.lastname: Dangel
authors.forename: R I
authors.initials: RI
authors.lastname: Kelley
authors.forename: W
authors.initials: W
authors.lastname: Zhao
authors.forename: P
authors.initials: P
authors.lastname: Denny
authors.forename: M
authors.initials: M
authors.lastname: Botcherby
authors.forename: B
authors.initials: B
authors.lastname: Cattanach
authors.forename: J
authors.initials: J
authors.lastname: Peters
authors.forename: P R
authors.initials: PR
authors.lastname: Hunsicker
authors.forename: A M
authors.initials: AM
authors.lastname: Mallon
authors.forename: M A
authors.initials: MA
authors.lastname: Strivens
authors.forename: R
authors.initials: R
authors.lastname: Bate
authors.forename: W
authors.initials: W
authors.lastname: Miller
authors.forename: M
authors.initials: M
authors.lastname: Rhodes
authors.forename: S D
authors.initials: SD
authors.lastname: Brown
authors.forename: G E
authors.initials: GE
authors.lastname: Herman
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000235:genetics*; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005091:Exons; D005124:Eye Abnormalities / Q000201:enzymology / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D012729:Sex Chromosome Aberrations; D012867:Skin / Q000378:metabolism; D012868:Skin Abnormalities / Q000201:enzymology / Q000235:genetics; D014960:X Chromosome
chemical_list: D015096:3-Hydroxysteroid Dehydrogenases; C515670:Nsdhl protein, mouse