Identification of two novel mutations in the murine Nsdhl sterol dehydrogenase gene and development of a functional complementation assay in yeast.
Nsdhl is a 3beta-hydroxysterol dehydrogenase that is involved in the removal of C-4 methyl groups in the cholesterol biosynthetic pathway. Mutations in this gene are associated with the X-linked male lethal mouse mutations bare patches (Bpa) and striated (Str) and human CHILD syndrome. We have now detected the missense mutations V53D and A94T in conserved amino acids in two additional Bpa alleles. The latter alters the same amino acid as a missense mutation found in two unrelated CHILD patients, strongly suggesting that differences in the phenotype between Bpa mice and females with CHILD syndrome are unlikely to be explained by different types or sites of mutations. We have also demonstrated that the mouse NSDHL protein can rescue the lethality of erg26 deficient cells of Saccharomyces cerevisiae that lack the yeast ortholog, substantiating the role of NSDHL as a C-3 sterol dehydrogenase. Using this in vivo assay, we have demonstrated that two Str alleles function as hypomorphs, while three Bpa and one Str allele provide no complementation or rescue.
Department of Pediatrics, Center for Molecular and Human Genetics, Columbus Children's Research Institute, 700 Children's Dr Rm W403, Columbus, OH 43205, USA.
Marsha E
ME
Lucas
Qi
Q
Ma
David
D
Cunningham
Jo
J
Peters
Bruce
B
Cattanach
Martin
M
Bard
Bradley K
BK
Elmore
Gail E
GE
Herman
D015096:3-Hydroxysteroid Dehydrogenases; D000015:Abnormalities, Multiple / Q000201:enzymology / Q000235:genetics; D000818:Animals; D002784:Cholesterol / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005816:Genetic Complementation Test; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D016114:Ichthyosis, X-Linked / Q000235:genetics*; D008297:Male; D051379:Mice; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014960:X Chromosome / Q000235:genetics
D002784:Cholesterol; D015096:3-Hydroxysteroid Dehydrogenases; D006913:Hydroxysteroid Dehydrogenases; C478776:Nsdhl protein, human