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Homozygous <jats:italic>Tmc1<\/jats:italic><jats:sup>\u2206\/\u2206<\/jats:sup> mice are deaf, <jats:italic>Tmc2<\/jats:italic><jats:sup>\u2206\/\u2206<\/jats:sup> mice have normal hearing, and double homozygous <jats:italic>Tmc1<\/jats:italic><jats:sup>\u2206\/\u2206<\/jats:sup>; <jats:italic>Tmc2<\/jats:italic><jats:sup>\u2206\/\u2206<\/jats:sup> mice have deafness and profound vestibular dysfunction. These phenotypes are consistent with their different spatiotemporal expression patterns. <jats:italic>Tmc1<\/jats:italic> expression is persistent in cochlear and vestibular hair cells, whereas <jats:italic>Tmc2<\/jats:italic> expression is transient in cochlear hair cells but persistent in vestibular hair cells. On the basis of these findings, we hypothesized that persistent <jats:italic>Tmc2<\/jats:italic> expression in mature cochlear hair cells could restore auditory function in <jats:italic>Tmc1<\/jats:italic><jats:sup>\u2206\/\u2206<\/jats:sup> mice. To express <jats:italic>Tmc2<\/jats:italic> in mature cochlear hair cells, we generated a transgenic mouse line, Tg[P<jats:sub><jats:italic>Tmc1<\/jats:italic><\/jats:sub>::<jats:italic>Tmc2<\/jats:italic>], in which <jats:italic>Tmc2<\/jats:italic> cDNA is expressed under the control of the <jats:italic>Tmc1<\/jats:italic> promoter. The Tg[P<jats:sub><jats:italic>Tmc1<\/jats:italic><\/jats:sub>::<jats:italic>Tmc2<\/jats:italic>] transgene slightly but significantly restored hearing in young <jats:italic>Tmc1<\/jats:italic><jats:sup>\u2206\/\u2206<\/jats:sup> mice, though hearing thresholds were elevated with age. The elevation of hearing thresholds was associated with deterioration of sensory transduction in inner hair cells and loss of outer hair cell function. Although sensory transduction was retained in outer hair cells, their stereocilia eventually degenerated. These results indicate distinct roles and requirements for <jats:italic>Tmc1<\/jats:italic> and <jats:italic>Tmc2<\/jats:italic> in mature cochlear hair cells.<\/jats:p>","DOI":"10.1038\/s41598-018-29709-8","type":"journal-article","created":{"date-parts":[[2018,8,8]],"date-time":"2018-08-08T13:06:56Z","timestamp":1533733616000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Tmc2 expression partially restores auditory function in a mouse model of DFNB7\/B11 deafness caused by loss of Tmc1 function"],"prefix":"10.1038","volume":"8","author":[{"given":"Hiroshi","family":"Nakanishi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyoto","family":"Kurima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9746-3420","authenticated-orcid":false,"given":"Bifeng","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philine","family":"Wangemann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy S.","family":"Fitzgerald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwena\u00eblle S.","family":"G\u00e9l\u00e9oc","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey R.","family":"Holt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Griffith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,8,14]]},"reference":[{"key":"29709_CR1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/0378-5955(93)90255-Y","volume":"66","author":"BJ Dannhof","year":"1993","unstructured":"Dannhof, B. 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