{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:22:14Z","timestamp":1787584934242,"version":"build-2736575974"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["JARO"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      <jats:italic>MYO7A<\/jats:italic>\n                      is involved in several forms of deafness in humans and mice, and in this study we aimed to investigate if the hearing loss could be reversed after its onset.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A knockdown allele of\n                      <jats:italic>Myo7a<\/jats:italic>\n                      in the mouse\n                      <jats:italic>, Myo7a<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>tm1a<\/jats:italic>\n                      <\/jats:sup>\n                      , was characterised by recording ABR thresholds at ages from 4\u00a0weeks to 6\u00a0months old and measuring the amount of hair cell degeneration at 4\u00a0weeks old. Scanning electron microscopy was used to assess the condition of stereocilia bundles. A tamoxifen-inducible Flp recombinase was used to activate expression of\n                      <jats:italic>Myo7a<\/jats:italic>\n                      in\n                      <jats:italic>Myo7a<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>tm1a\/tm1a<\/jats:italic>\n                      <\/jats:sup>\n                      homozygotes at 4\u00a0weeks old by excising the transcription disruption cassette in the tm1a allele allowing expression of the\n                      <jats:italic>Myo7a<\/jats:italic>\n                      gene, and ABRs were recorded before and after activation of the gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Myo7a<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>tm1a<\/jats:italic>\n                      <\/jats:sup>\n                      was found to be a recessive allele causing reduced transcription and early onset profound deafness. Some hair cell loss was found at 4\u00a0weeks old, and scanning electron microscopy showed\n                      <jats:italic>Myo7a<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>tm1a<\/jats:italic>\n                      <\/jats:sup>\n                      severely affects stereocilia morphology and organisation. Activation of\n                      <jats:italic>Myo7a<\/jats:italic>\n                      expression at 4\u00a0weeks old results in very small improvements in ABR thresholds of\n                      <jats:italic>Myo7a<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>tm1a\/tm1a<\/jats:italic>\n                      <\/jats:sup>\n                      mice at 12 and 18\u00a0kHz at 6 and 8\u00a0weeks old but there were no responses to sound by 14\u00a0weeks old.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>It is likely to be challenging to reverse hearing loss due to very early developmental defects of stereocilia organisation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10162-026-01050-2","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T17:00:37Z","timestamp":1776704437000},"page":"521-535","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Limited Potential to Reverse Deafness Caused by Mutation of Myo7a"],"prefix":"10.1007","volume":"27","author":[{"given":"Daniel R.","family":"Pentland","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Blackburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Witting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darcey A.","family":"Kirwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8019-5359","authenticated-orcid":false,"given":"Karen P.","family":"Steel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"1050_CR1","doi-asserted-by":"publisher","first-page":"11476","DOI":"10.1073\/pnas.1104161108","volume":"108","author":"M Grati","year":"2011","unstructured":"Grati M, Kachar B (2011) Myosin VIIa and sans localization at stereocilia upper tip-link density implicates these Usher syndrome proteins in mechanotransduction. 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