{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:26:03Z","timestamp":1788881163069,"version":"build-2803163510"},"reference-count":37,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,2,10]]},"abstract":"<jats:p>\n            Gap junction gene\n            <jats:italic>GJB2<\/jats:italic>\n            (Cx26) mutations cause &gt;50% of nonsyndromic hearing loss. Its recessive hetero-mutation carriers, who have no deafness, occupy ~10 to 20% of the general population. Here, we report an unexpected finding that these heterozygote carriers have hearing oversensitivity, and active cochlear amplification increased. Mouse models show that Cx26 hetero-deletion reduced endocochlear potential generation in the cochlear lateral wall and caused outer hair cell electromotor protein prestin compensatively up-regulated to increase active cochlear amplification and hearing sensitivity. The increase of active cochlear amplification also increased sensitivity to noise; exposure to daily-level noise could cause Cx26\n            <jats:sup>+\/\u2212<\/jats:sup>\n            mice permanent hearing threshold shift, leading to hearing loss. This study demonstrates that Cx26 recessive heterozygous mutations are not \u201charmless\u201d for hearing as previously considered and can cause hyperacusis-like hearing oversensitivity. The data also indicate that\n            <jats:italic>GJB2<\/jats:italic>\n            hetero-mutation carriers are vulnerable to noise and should avoid noise exposure in daily life.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adf4144","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T18:57:26Z","timestamp":1675882646000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":16,"title":["Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noise"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9346-3159","authenticated-orcid":true,"given":"Li-Man","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA."},{"name":"Department of Surgery\u2013Otolaryngology, Yale University Medical School, 310 Cedar Street, New Haven, CT 06510, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0490-4280","authenticated-orcid":true,"given":"Chun","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA."},{"name":"Hearing Function Testing Center, Shenzhen Maternity and Child Healthcare Hospital, 3012 Fuqiang Road, Shenzhen 518017, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6076-1141","authenticated-orcid":true,"given":"Jin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9335-9420","authenticated-orcid":true,"given":"Shu","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1189-2142","authenticated-orcid":true,"given":"Hong-Bo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA."},{"name":"Department of Surgery\u2013Otolaryngology, Yale University Medical School, 310 Cedar Street, New Haven, CT 06510, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2741\/3910"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24332"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31804d2371"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.281.23.2211"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-008-0342-7"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2004.00325.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.9.1605"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-005-0832-x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00186783"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007923"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/20686"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21113"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.04.016"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep15647"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.08.002"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2806"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.05.137"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00468.2021"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10916"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004410051192"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-008-0641-5"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00202"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2012.08.085"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.10.061"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.028324"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181d0d42b"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1222"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc030327"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00162"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8195-y"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00959.2004"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep10762"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)01626-8"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002320001051"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19051332"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01532-w"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.04.017"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adf4144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:42:34Z","timestamp":1704836554000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adf4144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,10]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,2,10]]}},"alternative-id":["10.1126\/sciadv.adf4144"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adf4144","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,10]]},"assertion":[{"value":"2022-10-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadf4144"}}