Connexin30 null and conditional connexin26 null mice display distinct pattern and time course of cellular degeneration in the cochlea

• Type of Material: Article
• Authors: Yu Sun, Emory University; Wenxue Tang, Emory University; Qing Chang, Emory University; Yunfeng Wang, Emory University; Weijia Kong, Huazhong University of Science and Technology; Xi Lin, Emory University
• Language: English
• Date: 2009-10-20
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Wiley-Liss, Inc.
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/cne.22117/abstract
• Title of Journal or Parent Work: Journal of Comparative Neurology
• ISSN: 0021-9967
• Volume: 516
• Issue: 6
• Start Page: 569
• End Page: 579
• Grant/Funding Information: W. Tang received grants from NIDCD (R21 DC008672) and the Deafness Research Foundation.; This study was supported by grants to X. Lin from NIDCD (RO1-DC006483 and R21-DC008353), National Natural Science Foundation (30728029) of China and the Woodruff Foundation.; Y. Sun and Y. Wang were partially supported by grants from China Scholarship Council (grant#:200710187 and 2008610021).
• Keywords: spiral ganglion neuron; neuronal degeneration; hair cells; genetic deafness; mouse model; connexin26 mutation; connexin30 mutation
• Research Categories: Biology, Neuroscience

Abstract

Mutations in connexin26 (Cx26) and Cx30 are the most common cause of non-syndromic inherited deafness in humans. To understand underlying molecular mechanisms, we investigated the pattern and time course of cellular degeneration in the cochlea of conditional Cx26 (cCx26) null and Cx30 null mice. In cCx26 null mice, initial degeneration was observed around postnatal day 14 in outer hair cells (OHCs) and supporting cells surrounding the OHCs. All cells in the middle turn organ of Corti were lost one month after birth and degeneration gradually spread to the basal and apical turns. Most spiral ganglion (SG) neurons in the middle and basal turns disappeared in the first three months, while significant amounts of apical SG neurons survived. In the cochlea of Cx30 null mice, survival of most inner HCs, supporting cells and SG neurons was observed for up to eighteen months. The most severe degeneration was found in apical SG neurons and OHCs. OHC loss followed a slow time course and a base to apex gradient. Gross structures of the endolymphatic space and stria vascularis observed at the light microscope level were unchanged in either Cx null mouse models. This study revealed that cellular degeneration in the cochlea of cCx26 null mice was dramatically more rapid and widespread than that observed in Cx30 null mice. The radically different pathogenesis processes displayed by cCx26 and Cx30 null mice suggest heterogeneous underlying deafness mechanisms, despite of the coassembly of Cx26 and Cx30 in forming gap junctions in the cochlea.