Early developmental expression of connexin26 in the cochlea contributes to its dominate functional role in the cochlear gap junctions

• Type of Material: Article
• Authors: Yan Qu, Third Hospital of Hebei Medical University; Wenxue Tang, Emory University; Binfei Zhou, Emory University; Shoeb Ahmad, Emory University; Qing Chang, Emory University; Xi Lin, Emory University
• Language: English
• Date: 2012-01-06
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://ac.els-cdn.com/S0006291X11021140/1-s2.0-S0006291X11021140-main.pdf?_tid=145dc9ac-c2fd-11e2-b1de-00000aacb35d&acdnat=1369240480_2a93de80e03b8e385489cb332bbb0c2d
• Title of Journal or Parent Work: Biochemical and Biophysical Research Communications
• ISSN: 0006-291X
• Volume: 417
• Issue: 1
• Start Page: 245
• End Page: 250
• Grant/Funding Information: Tang also received grant support from NIDCD (R21 DC008672).; This study was supported by following grants to X.Lin from National Institute on Deafness and other Communicative Disorders: NIDCD 4R33DC010476, R01DC010204 and RO1 DC006483.
• Keywords: hereditary deafness; functional studies; connexin26; hearing rescue; gap junctions; mouse model; connexin30
• Research Categories: Biology, Cell

Abstract

Mutations in Gjb2 and Gjb6 genes, coding for connexin26 (Cx26) and Cx30 proteins respectively, are linked to about half of all cases of human autosomal non-syndromic prelingual deafness. Molecular mechanisms of the hearing impairments, however, are unclear. Most cochlear gap junctions (GJs) are co-assembled from Cx26 and Cx30 and deletion of either one of them causes deafness. Our previous studies have shown that normal hearing is possible in the absence of the Cx30 gene when Cx26 is over-expressed. To further test unique functional requirements for various types of connexins in the hearing, we investigated whether the hearing in the conditional Cx26 (cCx26) null mice could be rescued by genetically over-expressing Cx30. Multiple lines of control and experimental mouse models were used. Auditory brainstem response (ABR) measurements showed normal hearing in targeted gene deletion mice when the deleted Cx26 or Cx30 was transgenically expressed from integrated bacterial artificial chromosome (BAC), demonstrating the effectiveness of the BAC rescue approach. In contrast, severe hearing loss was found in cCx26 null mice in which Cx30 was over-expressed. Morphology observations were consistent with the ABR data. Cochleae of cCx26 null mice with and without the transgenic over-expression of Cx30 both showed the typical immature feature of postnatal cochlear development-the closed tunnel of Corti. Immunolabeling data and Western blot quantification indicated that the Cx26 protein expression preceded that of Cx30 during the early postnatal period in the cochlea. Null expression of Cx26 may therefore uniquely result in a transient period when a total elimination of GJs in functionally-important regions of the developing cochlea is possible. We conclude that Cx26 plays an essential role in the development of the auditory sensory epithelium and its unique developmental functions required for normal hearing is not replaceable by Cx30.