Ultrastructural pathological changes in the cochlear cells of connexin 26 conditional knockout mice

• Type of Material: Article
• Authors: Lan Lin, Fudan University; Yun Wang, Emory University; Shu-Yi Wang, Fudan University; Shao-Feng Liu, Fudan University; Zhang Yu, Fudan University; Lin Xi, Emory University; Hua-Wei Li, Fudan University
• Language: English
• Date: 2013-10-01
• Publisher: Spandidos Publications
• Publication Version: Final Published Version
• Copyright Statement: © Spandidos Publications 2013. All rights reserved.
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.3892/mmr.2013.1614
• Title of Journal or Parent Work: Molecular Medicine Reports
• Volume: 8
• Issue: 4
• Start Page: 1029
• End Page: 1036
• Grant/Funding Information: This study was supported by grants from the Major State Basic Research Development Program of China (973 Program; no. 2011CB504506), the National Natural Science Foundation of China (no. 81230019),; the Program for Changjiang Scholars and Innovative Research Team in Universities (no. IRT1010), the Medical Guiding Fund of the Science and Technology Commission of Shanghai Municipality (no. 10411962100), the Program of Outstanding Shanghai Academic Leaders (no. 11XD1401300) and the Research Fund for the Doctoral Program of Higher Education of China (RFDP, no. 20120071110077).; Xi Lin and Huawei Li also received grant support from the National Science Foundation of China (no. 30728029).; The study was supported also by grants to Yunfeng Wang from the National Nature Science Foundation of China (no. 81100721) and to Xi Lin from the National Institute on Deafness and other Communication Disorders (nos. NIDCD 4R33DC010476 and RO1 DC006483).
• Keywords: Mutations; Research & Experimental Medicine; Organ; Postnatal development; Death; Hearing impairment; Expression; cochlea; Ablation; Gene; Oncology; connexin 26; Science & Technology; gene knockout; ultrastructural morphology; Life Sciences & Biomedicine; Corti; Medicine, Research & Experimental; Deafness
• Research Categories: Biology, Molecular; Health Sciences, Oncology; Biology, Genetics; Health Sciences, Pathology

Abstract

Mutations in the gene of connexin 26 (Cx26) are the most common cause of human non-syndromic hereditary deafness. The pathogenesis of deafness caused by Cx26 remains uncertain. To explore the basic mechanism underlying Cx26 null mutations, ultrastructural changes and a number of marker proteins in the cochlear sensory epithelium of Cx26 conditional knockout mice were observed in the current study. Cochlear specimens were obtained from Cx26 conditional knockout mice (cCx26ko), while wild-type mice served as controls. Antibodies against the pillar cell marker P75, the supporting cell marker prox1 and hair cell markers myosin 6 and phalloidin were labeled in different cells of the cochlear sensory epithelium of cochlear cryosections. The ultrastructural morphology of cochlear sensory epithelium was observed using transmission electron microscopy. Following the observation of cochlear sensory epithelium cell markers for hair cells and supporting cells, no significant changes were observed at the early stage, while the tunnel of the organ of Corti and Nuel's space was not developed prior to hearing onset in cCx26 knockout mice. Cell death was observed from postnatal day 10 (P10). The only region of surviving cells observed in the cochlea was the Hensen cell region, where microglia-like cells appeared following P180. Overall, the present study showed an abnormal ultrastructural morphology in the cochlear sensory epithelium in cCx26ko mice. Microglia-like cells may be involved in the process of cell degeneration in cCx26ko mice.