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Article: Functional analysis of a dominant mutation of human connexin26 associated with nonsyndromic deafness

TitleFunctional analysis of a dominant mutation of human connexin26 associated with nonsyndromic deafness
Authors
KeywordsCochlea
Connexin
Deafness
Gap junction
Genetic disease
Mutation
Issue Date2001
Citation
Cell Communication And Adhesion, 2001, v. 8 n. 4-6, p. 425-431 How to Cite?
AbstractCx26 has been implicated in dominant (DFNA3) and recessive (DFNB1) forms of nonsyndromic sensorineural deafness. While most homozygous DFNB1 Cx26 mutations result in a simple loss of channel activity, it is less clear how heterozygous mutations in Cx26 linked to DFNA3 cause hearing loss. We have tested the ability of one dominant mutation (W44C) to interfere with wild-type human Cx26 (HCx26wt). HCx26wt induced robust electrical conductance between paired oocytes, and facilitated dye transfer between transfected HeLa cells. In contrast, oocyte pairs injected with only W44C were not electrically coupled above background levels, and W44C failed to dye couple transfected HeLa cells. Moreover, W44C dramatically inhibited intercellular conductance of HCx26wt when co-expressed in an equal ratio, and the low levels of residual conductance displayed altered gating properties. A nonfunctional recessive mutation (W77R) did not inhibit the ability of HCx26wt to form functional channels when co-injected in the same oocyte pairs, nor did it alter HCx26wt gating. These results provide evidence for a functional dominant negative effect of the W44C mutant on HCx26wt and explain how heterozygous Cx26 mutations could contribute to autosomal dominant deafness, by resulting in a net loss, and/or alteration, of Cx26 function.
Persistent Identifierhttp://hdl.handle.net/10722/132714
ISSN
2003 Impact Factor: 1.289
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorBruzzone, Ren_HK
dc.contributor.authorGomès, Den_HK
dc.contributor.authorDenoyelle, Fen_HK
dc.contributor.authorDuval, Nen_HK
dc.contributor.authorPerea, Jen_HK
dc.contributor.authorVeronesi, Ven_HK
dc.contributor.authorWeil, Den_HK
dc.contributor.authorPetit, Cen_HK
dc.contributor.authorGabellec, MMen_HK
dc.contributor.authorD'Andrea, Pen_HK
dc.contributor.authorWhite, TWen_HK
dc.date.accessioned2011-03-28T09:28:29Z-
dc.date.available2011-03-28T09:28:29Z-
dc.date.issued2001en_HK
dc.identifier.citationCell Communication And Adhesion, 2001, v. 8 n. 4-6, p. 425-431en_HK
dc.identifier.issn1061-5385en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132714-
dc.description.abstractCx26 has been implicated in dominant (DFNA3) and recessive (DFNB1) forms of nonsyndromic sensorineural deafness. While most homozygous DFNB1 Cx26 mutations result in a simple loss of channel activity, it is less clear how heterozygous mutations in Cx26 linked to DFNA3 cause hearing loss. We have tested the ability of one dominant mutation (W44C) to interfere with wild-type human Cx26 (HCx26wt). HCx26wt induced robust electrical conductance between paired oocytes, and facilitated dye transfer between transfected HeLa cells. In contrast, oocyte pairs injected with only W44C were not electrically coupled above background levels, and W44C failed to dye couple transfected HeLa cells. Moreover, W44C dramatically inhibited intercellular conductance of HCx26wt when co-expressed in an equal ratio, and the low levels of residual conductance displayed altered gating properties. A nonfunctional recessive mutation (W77R) did not inhibit the ability of HCx26wt to form functional channels when co-injected in the same oocyte pairs, nor did it alter HCx26wt gating. These results provide evidence for a functional dominant negative effect of the W44C mutant on HCx26wt and explain how heterozygous Cx26 mutations could contribute to autosomal dominant deafness, by resulting in a net loss, and/or alteration, of Cx26 function.en_HK
dc.languageengen_US
dc.relation.ispartofCell Communication and Adhesionen_HK
dc.subjectCochleaen_HK
dc.subjectConnexinen_HK
dc.subjectDeafnessen_HK
dc.subjectGap junctionen_HK
dc.subjectGenetic diseaseen_HK
dc.subjectMutationen_HK
dc.titleFunctional analysis of a dominant mutation of human connexin26 associated with nonsyndromic deafnessen_HK
dc.typeArticleen_HK
dc.identifier.emailBruzzone, R: bruzzone@hkucc.hku.hken_HK
dc.identifier.authorityBruzzone, R=rp01442en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid12064630-
dc.identifier.scopuseid_2-s2.0-0035757730en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035757730&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume8en_HK
dc.identifier.issue4-6en_HK
dc.identifier.spage425en_HK
dc.identifier.epage431en_HK
dc.identifier.isiWOS:000175984300053-
dc.identifier.scopusauthoridBruzzone, R=7006793327en_HK
dc.identifier.scopusauthoridGomès, D=7005538633en_HK
dc.identifier.scopusauthoridDenoyelle, F=7006400138en_HK
dc.identifier.scopusauthoridDuval, N=7003504203en_HK
dc.identifier.scopusauthoridPerea, J=7004184669en_HK
dc.identifier.scopusauthoridVeronesi, V=6701534503en_HK
dc.identifier.scopusauthoridWeil, D=7103234861en_HK
dc.identifier.scopusauthoridPetit, C=7202973256en_HK
dc.identifier.scopusauthoridGabellec, MM=6603571362en_HK
dc.identifier.scopusauthoridD'Andrea, P=7005979859en_HK
dc.identifier.scopusauthoridWhite, TW=35499703300en_HK

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