title: Cell degeneration is not a primary causer for Connexin26 (GJB2) deficiency associated hearing loss.
abstract: Connexin26 (Cx26, GJB2) mutations can induce congenital deafness and are responsible for ∼50% of nonsyndromic hearing loss in children. Mouse models show that Cx26 deficiency induces cochlear development disorder, hair cell loss, and spiral ganglion (SG) neuron degeneration. Hair cell loss and cell degeneration have been considered as a primary causer responsible for Cx26 deficiency associated hearing loss. In this study, by coincidental examination of cochlear postnatal development with recording of auditory brainstem response (ABR) and hair cell function, we found that occurrence of hearing loss in Cx26 knockout (KO) mice was ahead of hair cell loss and cochlear cell degeneration. ABR was absent at the whole-frequency range (8-40 kHz) after birth. However, cochlear cells including SG neurons had no significant degeneration throughout postnatal development. Severe cochlear hair cell loss and SG neuron degeneration were only visible in middle and basal turns, i.e., in middle and high frequency regions, in the adult Cx26 KO mouse cochlea. Functional tests show that hair cells in Cx26 KO mice functioned normally; outer hair cells retained electromotility. These data suggest that cell degeneration is not a primary causer of Cx26 deficiency associated hearing loss. Some mechanisms other than cell degeneration, such as cochlear development disorders, may play an essential role in this common hereditary deafness.
authors.affiliation: Department of Otolaryngology, University of Kentucky Medical School, Lexington, KY 40536, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Liang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Liang
authors.initials: L
authors.lastname: Zong
authors.forename: Guang-Jin
authors.initials: GJ
authors.lastname: Lu
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Zhao
mesh_terms: D000818:Animals; D003051:Cochlea / Q000473:pathology*; D000072259:Connexin 26; D017630:Connexins / Q000172:deficiency / Q000235:genetics*; D003638:Deafness / Q000151:congenital / Q000235:genetics* / Q000473:pathology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D018408:Patch-Clamp Techniques
chemical_list: D017630:Connexins; C000607043:Gjb2 protein, mouse; D000072259:Connexin 26