Articolo in rivista, 2022, ENG, 10.3389/fcell.2022.950837

Connexin 30 deletion exacerbates cochlear senescence and age-related hearing loss

Paciello, Fabiola; Zorzi, Veronica; Raspa, Marcello; Scavizzi, Ferdinando; Grassi, Claudio; Mammano, Fabio; Fetoni, Anna Rita

Univ Cattolica Sacro Cuore; Fdn Policlin Univ A Gemelli IRCCS; CNR Inst Biochem & Cell Biol; Univ Padua; Univ Cattolica Sacro Cuore; Univ Naples Federico II

Pathogenic mutations in the Gjb2 and Gjb6 genes, encoding connexin 26 (Cx26) and connexin 30 (Cx30), respectively, have been linked to the most frequent monogenic hearing impairment, nonsyndromic hearing loss, and deafness DFNB1. It is known that Cx26 plays an important role in auditory development, while the role of Cx30 in hearing remains controversial. Previous studies found that partial deletion of Cx26 can accelerate age-related hearing loss (ARHL), a multifactorial complex disorder, with both environmental and genetic factors contributing to the etiology of the disease. Here, we investigated the role of Cx30 in cochlear-aging processes using a transgenic mouse model with total deletion of Cx30 (Cx30 delta delta mice), in which Cx30 was removed without perturbing the surrounding sequences. We show that these mice are affected by exacerbated ARHL, with increased morphological cochlear damage, oxidative stress, inflammation, and vascular dysfunctions. Overall, our data demonstrate that Cx30 deletion can be considered a genetic risk factor for ARHL, making cochlear structures more susceptible to aging processes.

Frontiers in Cell and Developmental Biology 10

Keywords

connexins, inner ear, inflammation, oxidative stress, vascular dysfunction, presbycusis, genetic risk factors

CNR authors

Raspa Marcello, Scavizzi Ferdinando

CNR institutes