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We previously demonstrated that variants in human MSRB3, an MSR family member, are associated with profound autosomal recessive prelingual non-syndromic deafness, DFNB74. To better understand the role of MSRB3 in the auditory pathway, we generated complete Msrb3 gene knockout mice. The Msrb3-deficient mice showed profound deafness by postnatal day 16, which was accompanied by morphological abnormalities including altered stereocilia bundle shape and cuticular plate degeneration, followed by hair cell apoptotic death. Although the absence of MSRB3 primarily affected the actin cytoskeleton, rootlets were present, and the localization of major F-actin stereocilia-core proteins was unaltered. Biochemical assays demonstrated that wild-type MSRB3, but not MSRB3 harboring p.Cys89Gly, the same variant reported for DFNB74, can repolymerize oxidized actin. Consistent with these results, we observed a decreased ratio of reduced\/total actin in the inner ears of Msrb3 knockout mice. These data suggest a protective role for MSRB3 in the maintenance and maturation of stereocilia and hair cells, a conserved mechanism aimed at maintaining actin redox dynamics in these sensory cells.<\/jats:p>","DOI":"10.1242\/dmm.052194","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T08:54:08Z","timestamp":1755593648000},"source":"Crossref","is-referenced-by-count":4,"title":["MSRB3 antioxidant activity is necessary for inner ear cuticular plate structure and hair bundle integrity"],"prefix":"10.1242","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5106-5192","authenticated-orcid":false,"given":"Gowri","family":"Nayak","sequence":"first","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center 1 Department of Developmental Biology , , Cincinnati, OH 45229 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4255-4699","authenticated-orcid":false,"given":"Elodie M.","family":"Richard","sequence":"additional","affiliation":[{"name":"University of Maryland 2 Department of Otorhinolaryngology Head and Neck Surgery, School of Medicine , , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Cheon","family":"Lee","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Harvard Medical School 3 Division of Genetics, Department of Medicine , , Boston, MA 02115 ,","place":["USA"]},{"name":"College of Life Sciences and Biotechnology, Korea University 4 , Seoul 02841 ,","place":["Republic of Korea"]},{"name":"Broad Institute 5 , Cambridge, MA 02142 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin P.","family":"Riordan","sequence":"additional","affiliation":[{"name":"National Institute on Deafness and Other Communication Disorders, NIH 6 Laboratory of Molecular Genetics , , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5030-9784","authenticated-orcid":false,"given":"Inna A.","family":"Belyantseva","sequence":"additional","affiliation":[{"name":"National Institute on Deafness and Other Communication Disorders, NIH 6 Laboratory of Molecular Genetics , , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8366-8935","authenticated-orcid":false,"given":"Bruno","family":"Manta","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Harvard Medical School 3 Division of Genetics, Department of Medicine , , Boston, MA 02115 ,","place":["USA"]},{"name":"Broad Institute 5 , Cambridge, MA 02142 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4614-6630","authenticated-orcid":false,"given":"Thomas B.","family":"Friedman","sequence":"additional","affiliation":[{"name":"National Institute on Deafness and Other Communication Disorders, NIH 6 Laboratory of Molecular Genetics , , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0372-7016","authenticated-orcid":false,"given":"Vadim N.","family":"Gladyshev","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Harvard Medical School 3 Division of Genetics, Department of Medicine , , Boston, MA 02115 ,","place":["USA"]},{"name":"Broad Institute 5 , Cambridge, MA 02142 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8645-4761","authenticated-orcid":false,"given":"Saima","family":"Riazuddin","sequence":"additional","affiliation":[{"name":"University of Maryland 2 Department of Otorhinolaryngology Head and Neck Surgery, School of Medicine , , Baltimore, MD 21201 ,","place":["USA"]},{"name":"School of Medicine, University of Maryland 7 Department of Molecular Biology and Biochemistry , , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"2025081915541827200_DMM052194C1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.ajhg.2010.11.010","article-title":"Functional null mutations of MSRB3 encoding methionine sulfoxide reductase are associated with human deafness DFNB74","volume":"88","author":"Ahmed","year":"2011","journal-title":"Am. 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