| Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus-Merzbacher-like disease. | |
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MedLine Citation:
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PMID: 17344063 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recessive mutations in GJA12/Cx47, the gene encoding the gap junction protein connexin47 (Cx47), cause Pelizaeus-Merzbacher-like disease (PMLD), which is characterized by severe CNS dysmyelination. Three missense PMLD mutations, P87S, Y269D and M283T, were expressed in communication-incompetent HeLa cells, and in each case the mutant proteins appeared to at least partially accumulate in the ER. Cells expressing each mutant did not pass Lucifer Yellow or neurobiotin in scrape loading assays, in contrast to robust transfer in cells expressing wild type Cx47. Dual whole-cell patch clamping of transfected Neuro2A cells demonstrated that none of the mutants formed functional channels, in contrast to wild type Cx47. Immunostaining sections of primate brains demonstrated that oligodendrocytes express Cx47, which is primarily localized to their cell bodies. Thus, the Cx47 mutants associated with PMLD likely disrupt the gap junction coupling between astrocytes and oligodendrocytes. |
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Authors:
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Jennifer L Orthmann-Murphy; Alan D Enriquez; Charles K Abrams; Steven S Scherer |
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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: 2007-01-25 |
Journal Detail:
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Title: Molecular and cellular neurosciences Volume: 34 ISSN: 1044-7431 ISO Abbreviation: Mol. Cell. Neurosci. Publication Date: 2007 Apr |
Date Detail:
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Created Date: 2007-04-02 Completed Date: 2007-06-22 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 9100095 Medline TA: Mol Cell Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 629-41 Citation Subset: IM |
Affiliation:
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Department of Neurology, University of Pennsylvania School of Medicine, Room 464 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104-6077, USA. lorthman@mail.med.upenn.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Astrocytes / metabolism Blotting, Western Brain / metabolism Cell Communication / genetics* Connexins / genetics* Endoplasmic Reticulum / metabolism Gap Junctions / genetics*, metabolism Hela Cells Humans Immunohistochemistry Macaca mulatta Molecular Sequence Data Mutation Oligodendroglia / metabolism Patch-Clamp Techniques Pelizaeus-Merzbacher Disease / genetics* Polymerase Chain Reaction Transfection |
| Grant Support | |
ID/Acronym/Agency:
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AG 00255/AG/NIA NIH HHS; F30 NS054363-01/NS/NINDS NIH HHS; K02 NS050345-02/NS/NINDS NIH HHS; NS043560/NS/NINDS NIH HHS; NS050345/NS/NINDS NIH HHS; NS050705/NS/NINDS NIH HHS; NS054363/NS/NINDS NIH HHS; NS42878/NS/NINDS NIH HHS; R01 NS042878-05/NS/NINDS NIH HHS; R01 NS050705-02/NS/NINDS NIH HHS; R01 NS055284-01A1/NS/NINDS NIH HHS; T32 AG000255-08/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Connexins; 0/connexin 47 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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