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Author Notes:

To whom correspondence should be addressed. E-mail: xlin2@emory.edu

Edited by Michael V. L. Bennett, Albert Einstein College of Medicine, Bronx, NY, and approved November 28, 2006

Author contributions: S.A. and W.T. contributed equally to this work; X.L. designed research; S.A., W.T., Q.C., and Y.Q. performed research; Y.L. contributed new reagents/analytic tools; S.A., W.T., Y.L., G.S., K.W., P.C., and X.L. analyzed data; and S.A., W.T., G.S., K.W., P.C., and X.L. wrote the paper.

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Research Funding:

This study was supported by the National Institute on Deafness and Other Communicative Disorders (Grants R01-DC04709 and RO1-DC006483, to X.L.) and the Woodruff Foundation (to X.L.). Work at the University of Bonn was supported by grants from the German Research Association and the Fritz Thyssen Foundation (to K.W.).

Keywords:

  • gap junction
  • hearing rescue
  • hereditary deafness

Restoration of connexin26 protein level in the cochlea completely rescues hearing in a mouse model of human connexin30-linked deafness

Tools:

Journal Title:

Proceedings of the National Academy of Sciences

Volume:

Volume 104, Number 4

Publisher:

, Pages 1337-1341

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Mutations in genes coding for connexin26 (Cx26) and/or Cx30 are linked to approximately half of all cases of human autosomal nonsyndromic prelingual deafness. Cx26 and Cx30 are the two major Cx isoforms found in the cochlea, and they coassemble to form hybrid (heteromeric and heterotypic) gap junctions (GJs). This molecular arrangement implies that homomeric GJs would remain in the cochlea if one of the coassembly partners were mutated resulting in null expression. We generated mice in which extra copies of the Cx26 gene were transgenically expressed from a modified bacterial artificial chromosome in a Cx30−/− background. In the absence of the Cx30 gene, Cx26 expressed from extra alleles completely restored hearing sensitivity and prevented hair cell death in deaf Cx30−/− mice. The results indicated that hybrid GJs consisting of Cx26 and Cx30 were not essential for normal hearing in mice and suggested that up-regulation of Cx26 or slowing down its protein degradation might be a therapeutic strategy to prevent and treat deafness caused by Cx30 mutations.

Copyright information:

© 2007 by The National Academy of Sciences of the USA

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