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Recent genome-wide association studies (GWAS) linked variation in several genes with ARHL risk, including\n                    <jats:italic>KLHDC7B<\/jats:italic>\n                    , a gene of unknown function not previously linked to hearing. We demonstrate\n                    <jats:italic>Klhdc7b<\/jats:italic>\n                    is expressed exclusively in sensory hair cells in mouse cochlea. Utilizing two independent mouse knockout models (\n                    <jats:italic>Klhdc7b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>IMPC-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    and\n                    <jats:italic>Klhdc7b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Regn<\/jats:italic>\n                      \u0394\/\u0394\n                    <\/jats:sup>\n                    ) we find that absence of\n                    <jats:italic>Klhdc7b<\/jats:italic>\n                    leads to severe early-onset, progressive hearing loss. Hair cells appear to develop normally, but outer hair cells are progressively lost from base-to-apex of the cochlea, a common pathology in ARHL. These results suggest KLHDC7B is required for maintenance rather than development, of auditory function. The validation in mouse of a human ARHL GWAS association suggests other novel candidates should be investigated. Our work provides two mouse models to study KLHDC7B function, and for development of therapeutic tools for ARHL.\n                  <\/jats:p>","DOI":"10.1038\/s42003-025-09349-1","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T16:15:59Z","timestamp":1765988159000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cross-species validation of a human age-related hearing loss candidate KLHDC7B\u00a0as essential for mammalian hearing"],"prefix":"10.1038","volume":"9","author":[{"given":"Alexandra M.","family":"Kaufman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Silver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto A.","family":"Donnianni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4655-1778","authenticated-orcid":false,"given":"Carlos","family":"Aguilar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingzi","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6705-5263","authenticated-orcid":false,"given":"Anwen","family":"Bullen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma","family":"Corona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"van Soldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2265-5580","authenticated-orcid":false,"given":"Nilay","family":"Vora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gervasio","family":"Batista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luz","family":"Cortes-Burgos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Copeland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elika","family":"Fallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Lehmkuhl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Cancelarich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara","family":"Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Di Battista Miani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaylen","family":"Mumphrey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan D.","family":"Croll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnathon R.","family":"Walls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Germino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7971-445X","authenticated-orcid":false,"given":"Michael R.","family":"Bowl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan C.","family":"Drummond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4421-2043","authenticated-orcid":false,"given":"Sally J.","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"9349_CR1","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.1016\/S0140-6736(17)31363-6","volume":"390","author":"G Livingston","year":"2017","unstructured":"Livingston, G. et al. 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