| Cholesterol metabolism is required for intracellular hedgehog signal transduction in vivo. | |
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MedLine Citation:
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PMID: 21912524 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We describe the rudolph mouse, a mutant with striking defects in both central nervous system and skeletal development. Rudolph is an allele of the cholesterol biosynthetic enzyme, hydroxysteroid (17-beta) dehydrogenase 7, which is an intriguing finding given the recent implication of oxysterols in mediating intracellular Hedgehog (Hh) signaling. We see an abnormal sterol profile and decreased Hh target gene induction in the rudolph mutant, both in vivo and in vitro. Reduced Hh signaling has been proposed to contribute to the phenotypes of congenital diseases of cholesterol metabolism. Recent in vitro and pharmacological data also indicate a requirement for intracellular cholesterol synthesis for proper regulation of Hh activity via Smoothened. The data presented here are the first in vivo genetic evidence supporting both of these hypotheses, revealing a role for embryonic cholesterol metabolism in both CNS development and normal Hh signaling. |
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Authors:
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Rolf W Stottmann; Annick Turbe-Doan; Pamela Tran; Lisa E Kratz; Jennifer L Moran; Richard I Kelley; David R Beier |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-09-01 |
Journal Detail:
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Title: PLoS genetics Volume: 7 ISSN: 1553-7404 ISO Abbreviation: PLoS Genet. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-09-13 Completed Date: 2012-01-12 Revised Date: 2012-04-26 |
Medline Journal Info:
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Nlm Unique ID: 101239074 Medline TA: PLoS Genet Country: United States |
Other Details:
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Languages: eng Pagination: e1002224 Citation Subset: IM |
Affiliation:
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Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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17-Hydroxysteroid Dehydrogenases
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genetics*,
metabolism Animals Bone Development / genetics Cholesterol / genetics, metabolism* Ethylnitrosourea / pharmacology Hedgehog Proteins / metabolism* Mice Mice, Mutant Strains Mutagenesis Mutation Prosencephalon / abnormalities*, metabolism Receptors, G-Protein-Coupled / genetics, metabolism Signal Transduction |
| Grant Support | |
ID/Acronym/Agency:
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HD053198/HD/NICHD NIH HHS; HD36404/HD/NICHD NIH HHS; MH081187/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Hedgehog Proteins; 0/Receptors, G-Protein-Coupled; 0/Smo protein, mouse; 57-88-5/Cholesterol; 759-73-9/Ethylnitrosourea; EC 1.1.-/17-Hydroxysteroid Dehydrogenases; EC 1.1.1.51/3 (or 17)-beta-hydroxysteroid dehydrogenase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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