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Clarin-2 is essential for hearing by maintaining stereocilia integrity and function

ABSTRACT: Hearing relies on mechanically-gated ion channels present in the actin-rich stereocilia bundles at the apical surface of cochlear hair cells. Our knowledge of the mechanisms underlying the formation and maintenance of the sound-receptive structure is limited. Utilizing a large-scale forward genetic screen in mice, genome mapping, and gene complementation tests, we identified Clrn2 as a new deafness gene. The Clrn2clarinet/clarinet mice (p.Trp4* mutation) exhibit a progressive, early-onset hearing loss, with no overt retinal deficits. Utilizing data from the UK Biobank study we could show that CLRN2 is involved in human non-syndromic progressive hearing loss. Our in-depth morphological, molecular, and functional investigations establish that while it is not required for initial formation of cochlear sensory hair cell stereocilia bundles, clarin-2 is critical for maintaining normal bundle integrity and functioning. In the differentiating hair bundles, lack of clarin-2 leads to loss of mechanoelectrical transduction, followed by selective progressive loss of the transducing stereocilia. Together, our findings demonstrate a key role for clarin-2 in mammalian hearing, providing insights into the interplay between mechanoelectrical transduction and stereocilia maintenance.

SUBMITTER: Miss Lucy, A Dunbar

PROVIDER: S-SCDT-EMM-2019-10288 | biostudies-other |

REPOSITORIES: biostudies-other

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Clarin-2 is essential for hearing by maintaining stereocilia integrity and function.

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