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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,3,5]]},"abstract":"<jats:p>\n                    Inner ear hair cells are characterized by the F-actin-based stereocilia that are arranged into a staircase-like pattern on the apical surface of each hair cell. The tips of shorter-row stereocilia are connected with the shafts of their neighboring taller-row stereocilia through extracellular links named tip links, which gate mechano-electrical transduction (MET) channels in hair cells. Cadherin 23 (CDH23) forms the upper part of tip links, and its cytoplasmic tail is inserted into the so-called upper tip-link density (UTLD) that contains other proteins such as harmonin. The\n                    <jats:italic>Cdh23<\/jats:italic>\n                    gene is composed of 69 exons, and we show here that exon 68 is subjected to hair cell\u2013specific alternative splicing. Tip-link formation is not affected in genetically modified mutant mice lacking\n                    <jats:italic>Cdh23<\/jats:italic>\n                    exon 68. Instead, the stability of tip links is compromised in the mutants, which also suffer from progressive and noise-induced hearing loss. Moreover, we show that the cytoplasmic tail of CDH23(+68) but not CDH23(\u221268) cooperates with harmonin in phase separation\u2013mediated condensate formation. In conclusion, our work provides evidence that inclusion of\n                    <jats:italic>Cdh23<\/jats:italic>\n                    exon 68 is critical for the stability of tip links through regulating condensate formation of UTLD components.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2309656121","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T15:00:36Z","timestamp":1708959636000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":7,"title":["Disruption of\n                    <i>Cdh23<\/i>\n                    exon 68 splicing leads to progressive hearing loss in mice by affecting tip-link stability"],"prefix":"10.1073","volume":"121","author":[{"given":"Nana","family":"Li","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology and Key Laboratory for Experimental Teratology of the Ministry of Education, School of Life Sciences, Shandong University, Qingdao, Shandong 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Liu","sequence":"additional","affiliation":[{"name":"Chinese Institute for Brain Research, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dange","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Du","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology and Key Laboratory for Experimental Teratology of the Ministry of Education, School of Life Sciences, Shandong University, Qingdao, Shandong 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehui","family":"Xi","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology and Key Laboratory for Experimental Teratology of the Ministry of Education, School of Life Sciences, Shandong University, Qingdao, Shandong 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7168-9872","authenticated-orcid":false,"given":"Xiaoxi","family":"Wei","sequence":"additional","affiliation":[{"name":"Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingling","family":"Liu","sequence":"additional","affiliation":[{"name":"Chinese Institute for Brain Research, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"The Solomon H. 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