{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T13:46:38Z","timestamp":1782395198771,"version":"3.54.5"},"reference-count":37,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":61,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"crossref","award":["K08DC019716,K08DC016034,R01DC020574,ZIA DC000088,R01DC018785"],"award-info":[{"award-number":["K08DC019716,K08DC016034,R01DC020574,ZIA DC000088,R01DC018785"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005193","name":"American Academy of Otolaryngology-Head and Neck Surgery","doi-asserted-by":"crossref","award":["CORE grant"],"award-info":[{"award-number":["CORE grant"]}],"id":[{"id":"10.13039\/100005193","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Indiana University","award":["Biomedical Research Grant"],"award-info":[{"award-number":["Biomedical Research Grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,16]]},"abstract":"<jats:p>\n                    Pathogenic variants in the gene\n                    <jats:italic>TMPRSS3<\/jats:italic>\n                    are a common cause of hearing loss in humans, although the causal mechanisms remain unknown. Previous work has shown that\n                    <jats:italic>\n                      Tmprss3\n                      <jats:sup>Y260X\/Y260X<\/jats:sup>\n                    <\/jats:italic>\n                    mice exhibit normal hair cell development, mechanosensory transduction, and spiral ganglion patterning, but experience rapid hair cell death from P12 to P14 at the onset of hearing. Here, we demonstrate that\n                    <jats:italic>\n                      Tmprss3\n                      <jats:sup>Y260X\/Y260X<\/jats:sup>\n                    <\/jats:italic>\n                    mice display an early and temporary spike in endocochlear potential (EP) prior to the onset of hair cell death. In vitro experiments with cochlear explants from\n                    <jats:italic>\n                      Tmprss3\n                      <jats:sup>Y260X\/Y260X<\/jats:sup>\n                    <\/jats:italic>\n                    mice and in vivo studies with\n                    <jats:italic>\n                      Tmprss3\n                      <jats:sup>Y260X\/Y260X<\/jats:sup>\n                    <\/jats:italic>\n                    mice crossed with 2 different mutant models that lacked EP generation promoted hair cell survival. Furthermore, systemic administration of furosemide, a drug that reduces EP in vivo, reduced hair cell death in\n                    <jats:italic>\n                      Tmprss3\n                      <jats:sup>Y260X\/Y260X<\/jats:sup>\n                    <\/jats:italic>\n                    mice. These findings suggest that extracellular factors, including EP, play a role in TMPRSS3-related hair cell survival and hearing loss, and suggest that modulating EP could be a therapeutic strategy.\n                  <\/jats:p>","DOI":"10.1172\/jci186395","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T16:00:11Z","timestamp":1752768011000},"source":"Crossref","is-referenced-by-count":6,"title":["Endocochlear potential contributes to hair cell death in TMPRSS3 hearing loss"],"prefix":"10.1172","volume":"135","author":[{"given":"A. Eliot","family":"Shearer","sequence":"first","affiliation":[{"name":"Department of Otolaryngology and Communication Enhancement, Boston Children\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Department of Otolaryngology Head and Neck Surgery, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Siao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L.","family":"Rouse","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janmaris","family":"Marin Fermin","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin T.A.","family":"Booth","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, and"},{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Moawad","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine, Indiana University, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole Bianca","family":"Libiran","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine, Indiana University, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication Enhancement, Boston Children\u2019s Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7469-2909","authenticated-orcid":true,"given":"Michael","family":"Hoa","sequence":"additional","affiliation":[{"name":"Auditory Development and Restoration Program, Neurotology Branch, National Institutes on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafal","family":"Olszewski","sequence":"additional","affiliation":[{"name":"Auditory Development and Restoration Program, Neurotology Branch, National Institutes on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Yu","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas J.","family":"Totten","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2881-5714","authenticated-orcid":true,"given":"Bo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7182-8011","authenticated-orcid":true,"given":"Jeffrey R.","family":"Holt","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication Enhancement, Boston Children\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Department of Otolaryngology Head and Neck Surgery, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5749-6383","authenticated-orcid":true,"given":"Rick F.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-011-0282-3"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1159\/000528766"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2012.08.007"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2017.02.008"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/AUD.0000000000001386"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/MAO.0000000000002943"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-018-2793-2"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.08.006"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2022-108654"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.007"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds532"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.584928"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2278-19.2020"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3162-04.2004"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.190652"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402660101"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201210913"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00136.2009"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.008"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1121\/1.381736"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1515228112"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00312.2001"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(95)00133-X"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.05.014"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75238-8"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12030"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168953"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5432.1408"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2023.08.004"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.joto.2016.10.001"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004688"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/S1672-2930(09)50003-7"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10092254"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abi7629"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-011-9244-0"},{"key":"B36","unstructured":"Elkin LA, et al. Title, Paper presented at: UIST \u201821: The 34th Annual ACM Symposium on User Interface Software and Technology; October 10\u201314, 2021; Virtual Event, USA. https:\/\/dl.acm.org\/doi\/10.1145\/3472749.3474784 Accessed July 21, 2025"},{"key":"B37","unstructured":"Wobbrock J, et al. The Aligned Rank Transform for Nonparametric Factorial Analyses Using Only ANOVA Procedures. Paper presented at: CHI \u201811: CHI Conference on Human Factors in Computing Systems; May 7\u201312, 2011; Vancouver, British Columbia, Canada. https:\/\/dl.acm.org\/doi\/10.1145\/1978942.1978963 Accessed July 21, 2025"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/186395\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:57:22Z","timestamp":1779213442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/186395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,17]]},"references-count":37,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9,16]]},"published-print":{"date-parts":[[2025,9,16]]}},"alternative-id":["10.1172\/JCI186395"],"URL":"https:\/\/doi.org\/10.1172\/jci186395","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,17]]},"article-number":"e186395"}}