title: Connexin30 null and conditional connexin26 null mice display distinct pattern and time course of cellular degeneration in the cochlea.
abstract: Mutations in connexin26 (Cx26) and Cx30 are the most common cause of nonsyndromic inherited deafness in humans. To understand the 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 1 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 3 months, whereas 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 18 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 co-assembly of Cx26 and Cx30 in forming gap junctions in the cochlea.
authors: Department of Otolaryngology, Emory University School of Medicine, Atlanta, GA 30322-3030, USA.
authors: Yu
authors: Y
authors: Sun
authors: Wenxue
authors: W
authors: Tang
authors: Qing
authors: Q
authors: Chang
authors: Yunfeng
authors: Y
authors: Wang
authors: Weijia
authors: W
authors: Kong
authors: Xi
authors: X
authors: Lin
mesh_terms: D000375:Aging; D000818:Animals; D015153:Blotting, Western; D016923:Cell Death; D002470:Cell Survival; D003051:Cochlea / Q000473:pathology* / Q000503:physiopathology; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006199:Hair Cells, Auditory, Inner / Q000473:pathology / Q000502:physiology; D018072:Hair Cells, Auditory, Outer / Q000473:pathology / Q000502:physiology; D034381:Hearing Loss / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D006320:Hearing Tests; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000473:pathology / Q000502:physiology; D013136:Spiral Ganglion / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C100629:Gjb6 protein, mouse; D000072259:Connexin 26