Résumé
Methionine sulfoxide reductases (MSRs) are enzymes responsible for catalyzing the reduction of methionine sulfoxides. 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.