| Functional studies reveal new mechanisms for deafness caused by connexin mutations. | |
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MedLine Citation:
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PMID: 19169135 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Connexin26 (Cx26) and Cx30 are the major protein subunits forming gap junction (GJ) intercellular channels in the cochlea. Mutations in these 2 Cxs are the major cause of nonsyndromic early childhood deafness in humans. The underlying mechanism for cochlear abnormality is unclear. Here, we used targeted Cx30 gene deletion (Cx30-/-) mice to investigate molecular mechanisms responsible for Cx mutation-linked deafness. Our hypothesis is that specific loss of GJ-mediated biochemical coupling in the cochlea is sufficient to cause deafness. STUDY DESIGN: We compared: (1) expression of major cochlear GJ protein subunits, Cx26 and Cx30; and (2) biochemical coupling among cochlear supporting cells in the cochleae of wild type and Cx30-/- mice. METHODS: Immunolabeling was used to examine the expression of the remaining Cx protein expression in the cochlea of Cx30-/- mice. We also used a fluorescent dye diffusion assay performed on a novel flattened cochlear preparation to examine GJ-mediated metabolite transfer among cochlear supporting cells. RESULTS: Estimation of the residual ionic conductance indicated that considerable intercellular ionic coupling remained in the cochlea of Cx30-/- mice. Direct measurement of GJ-mediated biochemical coupling showed that the transfer of metabolites among cochlear supporting cells in Cx30-/- mice was severely reduced. CONCLUSION: Our data support that deficiency in GJ-mediated biochemical coupling is sufficient to cause Cx mutation-linked deafness. |
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Authors:
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Qing Chang; Wenxue Tang; Shoeb Ahmad; Benjamin Stong; Grace Leu; Xi Lin |
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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 |
Journal Detail:
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Title: Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Volume: 30 ISSN: 1537-4505 ISO Abbreviation: Otol. Neurotol. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-01-26 Completed Date: 2009-04-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100961504 Medline TA: Otol Neurotol Country: United States |
Other Details:
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Languages: eng Pagination: 237-40 Citation Subset: IM |
Affiliation:
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Department of Otolaryngology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cochlea / anatomy & histology, physiology Connexins / genetics* Deafness / genetics*, pathology* Diffusion Epithelium / pathology Fluorescent Dyes Gap Junctions / genetics Glucose / metabolism Mice Mice, Knockout Mutation / genetics*, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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R01-DC006483/DC/NIDCD NIH HHS; R03-DC008693/DC/NIDCD NIH HHS; R21-DC008353/DC/NIDCD NIH HHS; R21-DC008672/DC/NIDCD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Connexins; 0/Fluorescent Dyes; 0/Gjb6 protein, mouse; 50-99-7/Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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