Abstract
Connexin26 (Cx26, encoded by GJB2) mutations are the most common cause of non-syndromic deafness. GJB2 is thought to be involved in noise-induced hearing loss (NIHL). However, the role of Cx26 in NIHL is still obscure. To explore the association between Cx26 and NIHL, we established a Cx26 knockdown (KD) mouse model by conditional knockdown of Cx26 at postnatal day 18 (P18), and then we observed the auditory threshold and morphologic changes in these mice with or without noise exposure. The Cx26 KD mice did not exhibit substantial hearing loss and hair cell degeneration, while the Cx26 KD mice with acoustic trauma experienced higher hearing loss than simple noise exposure siblings and nearly had no recovery. Additionally, extensive outer hair cell loss and more severe destruction of the basal organ of Corti were observed in Cx26 KD mice after noise exposure. These data indicate that reduced Cx26 expression in the mature mouse cochlea may increase susceptibility to noise-induced hearing loss and facilitate the cell degeneration in the organ of Corti.
Highlights
GJB2 mutations are the most common causes of non-syndromic deafness and more than 100 GJB2 mutations are linked with hearing impairment
Gap junctions (GJs), which facilitate the exchange of ions, small molecules and second messengers, are arrays of intercellular channels that are composed of connexin protein subunits [1,2,3,4]
Due to the vital role of Cx26 in cochlear physiology, numerous studies have explored the correlation between the genetic basis of GJB2 mutations/polymorphisms and other types of hearing loss, such as noise-induced hearing loss (NIHL); the results have been contradictory
Summary
GJB2 mutations are the most common causes of non-syndromic deafness and more than 100 GJB2 mutations are linked with hearing impairment. Due to the vital role of Cx26 in cochlear physiology, numerous studies have explored the correlation between the genetic basis of GJB2 mutations/polymorphisms and other types of hearing loss, such as noise-induced hearing loss (NIHL); the results have been contradictory. Similar conclusions were drawn in Polish and Brazilian population [11,12] Another analysis of single nucleotide polymorphisms (SNPs) indicated that the GJB2 gene may be significantly associated with NIHL. Previous Cx26 null mice exhibited congenital severe hearing loss after birth when Cx26 was reduced during embryonic periods These mice were good models for congenital non-syndromic deafness but were not appropriate for noise exposure [15,16,17]. Our data suggests that normal hearing is maintained in mice when Cx26 is reduced in mature cochlea; loss of Cx26 exacerbates hearing loss and the cochlear cell degeneration that occurs after acoustic trauma
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