Document Detail


Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus-Merzbacher-like disease.
MedLine Citation:
PMID:  17344063     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jennifer L Orthmann-Murphy; Alan D Enriquez; Charles K Abrams; Steven S Scherer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-01-25
Journal Detail:
Title:  Molecular and cellular neurosciences     Volume:  34     ISSN:  1044-7431     ISO Abbreviation:  Mol. Cell. Neurosci.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-02     Completed Date:  2007-06-22     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  9100095     Medline TA:  Mol Cell Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  629-41     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
AG 00255/AG/NIA NIH HHS; F30 NS054363-01/NS/NINDS NIH HHS; K02 NS050345/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/NS/NINDS NIH HHS; R01 NS042878-05/NS/NINDS NIH HHS; R01 NS050705/NS/NINDS NIH HHS; R01 NS050705-02/NS/NINDS NIH HHS; R01 NS055284/NS/NINDS NIH HHS; R01 NS055284-01A1/NS/NINDS NIH HHS; T32 AG000255/AG/NIA NIH HHS; T32 AG000255-08/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Connexins; 0/connexin 47
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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