| First Author | Dunbar LA | Year | 2019 |
| Journal | EMBO Mol Med | Volume | 11 |
| Issue | 9 | Pages | e10288 |
| PubMed ID | 31448880 | Mgi Jnum | J:283627 |
| Mgi Id | MGI:6376373 | Doi | 10.15252/emmm.201910288 |
| Citation | Dunbar LA, et al. (2019) Clarin-2 is essential for hearing by maintaining stereocilia integrity and function. EMBO Mol Med 11(9):e10288 |
| abstractText | 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 Clrn2(clarinet/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 mechano-electrical 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 mechano-electrical transduction and stereocilia maintenance. |
