{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:06:18Z","timestamp":1785920778301,"version":"3.56.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DC015824"],"award-info":[{"award-number":["R01 DC015824"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010240","name":"Nancy Sayles Day Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010240","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010572","name":"Lauer Tinnitus Research Center, Massachusetts Eye and Ear","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010572","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Cochlin is the most abundant protein in the inner ear. To study its function in response to noise trauma, we exposed adolescent wild-type (<jats:italic>Coch<\/jats:italic><jats:italic><jats:sup>+\/+<\/jats:sup><\/jats:italic>) and cochlin knock-out (<jats:italic>Coch<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup>) mice to noise (8\u201316 kHz, 103 dB SPL, 2 h) that causes a permanent threshold shift and hair cell loss. Two weeks after noise exposure, <jats:italic>Coch<jats:sup>\u2013\/\u2013<\/jats:sup><\/jats:italic> mice had substantially less elevation in noise-induced auditory thresholds and hair cell loss than <jats:italic>Coch<\/jats:italic><jats:sup>+<\/jats:sup><jats:italic><jats:sup>\/<\/jats:sup><\/jats:italic><jats:sup>+<\/jats:sup> mice, consistent with cochlin deficiency providing protection from noise trauma. Comparison of pre-noise exposure thresholds of auditory brain stem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) in <jats:italic>Coch<jats:sup>\u2013\/\u2013<\/jats:sup><\/jats:italic> mice and <jats:italic>Coch<\/jats:italic><jats:sup>+<\/jats:sup><jats:italic><jats:sup>\/<\/jats:sup><\/jats:italic><jats:sup>+<\/jats:sup> littermates revealed a small and significant elevation in thresholds of <jats:italic>Coch<jats:sup>\u2013\/\u2013<\/jats:sup><\/jats:italic> mice, overall consistent with a small conductive hearing loss in <jats:italic>Coch<jats:sup>\u2013\/\u2013<\/jats:sup><\/jats:italic> mice. We show quantitatively that the pro-inflammatory component of cochlin, LCCL, is upregulated after noise exposure in perilymph of wild-type mice compared to unexposed mice, as is the enzyme catalyzing LCCL release, aggrecanase1, encoded by <jats:italic>Adamts4<\/jats:italic>. We further show that upregulation of pro-inflammatory cytokines in perilymph and cochlear soft-tissue after noise exposure is lower in cochlin knock-out than wild-type mice. Taken together, our data demonstrate for the first time that cochlin deficiency results in conductive hearing loss that protects against physiologic and molecular effects of noise trauma.<\/jats:p>","DOI":"10.3389\/fnmol.2021.670013","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T04:24:12Z","timestamp":1621830252000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Cochlin Deficiency Protects Against Noise-Induced Hearing Loss"],"prefix":"10.3389","volume":"14","author":[{"given":"Richard","family":"Seist","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas D.","family":"Landegger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahid G.","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasa","family":"Vasilijic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia C.","family":"Morton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantina M.","family":"Stankovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1097\/00129492-200205000-00015","article-title":"Clinical implications of inflammatory cytokines in the cochlea: a technical note.","volume":"23","author":"Adams","year":"2002","journal-title":"Otol. 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