Document Detail


Dominant Cx26 mutants associated with hearing loss have dominant-negative effects on wild type Cx26.
MedLine Citation:
PMID:  21040787     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Mutations in GJB2, the gene encoding the human gap junction protein connexin26 (Cx26), cause either non-syndromic hearing loss or syndromes affecting both hearing and skin. We have investigated whether dominant Cx26 mutants can interact physically with wild type Cx26. HeLa cells stably expressing wild type Cx26 were transiently transfected to co-express nine individual dominant Cx26 mutants; six associated with non-syndromic hearing loss (W44C, W44S, R143Q, D179N, R184Q, and C202F) and three associated with hearing loss and palmoplantar keratoderma (G59A, R75Q, and R75W). All mutants co-localized and co-immunoprecipitated with wild type Cx26, indicating that they interact physically, likely by forming admixed heteromeric/heterotypic channels. Furthermore, all nine mutants inhibited the transfer of calcein in cells stably expressing Cx26, demonstrating that they each have dominant effects on wild type Cx26. Taken together, these results show that dominant-negative effects of these Cx26 mutants likely contribute to the pathogenesis of hearing loss.
Authors:
Junxian Zhang; Steven S Scherer; Sabrina W Yum
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Publication Detail:
Type:  Journal Article     Date:  2010-10-30
Journal Detail:
Title:  Molecular and cellular neurosciences     Volume:  47     ISSN:  1095-9327     ISO Abbreviation:  Mol. Cell. Neurosci.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9100095     Medline TA:  Mol Cell Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  71-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pediatrics, Division of Neurology, The Children's Hospital of Philadelphia, USA.
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