title: Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells.
abstract: The mouse shaker-1 locus, Myo7a, encodes myosin VIIA and mutations in the orthologous gene in humans cause Usher syndrome type 1B or non-syndromic deafness. Myo7a is expressed very early in sensory hair cell development in the inner ear. We describe the effects of three mutations on cochlear hair cell development and function. In the Myo7a816SB and Myo7a6J mutants, stereocilia grow and form rows of graded heights as normal, but the bundles become progressively more disorganised. Most of these mutants show no gross electrophysiological responses, but some did show evidence of hair cell depolarisation despite the disorganisation of their bundles. In contrast, the original shaker-1 mutants, Myo7ash1, had normal early development of stereocilia bundles, but still showed abnormal cochlear responses. These findings suggest that myosin VIIA is required for normal stereocilia bundle organisation and has a role in the function of cochlear hair cells.
authors.affiliation: MRC Institute of Hearing Research, University Park, Nottingham NG7 2RD, UK.
authors.forename: T
authors.initials: T
authors.lastname: Self
authors.forename: M
authors.initials: M
authors.lastname: Mahony
authors.forename: J
authors.initials: J
authors.lastname: Fleming
authors.forename: J
authors.initials: J
authors.lastname: Walsh
authors.forename: S D
authors.initials: SD
authors.lastname: Brown
authors.forename: K P
authors.initials: KP
authors.lastname: Steel
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002923:Cilia / Q000648:ultrastructure; D017931:DNA Primers / Q000235:genetics; D004398:Dyneins; D004594:Electrophysiology; D006198:Hair Cells, Auditory / Q000254:growth & development* / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009154:Mutation; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics* / Q000502:physiology*
chemical_list: D017931:DNA Primers; C000631455:MYO7A protein, human; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; D009218:Myosins; D004398:Dyneins