title: A novel stereocilia defect in sensory hair cells of the deaf mouse mutant Tasmanian devil.
abstract: Stereocilia are specialized actin-filled, finger-like processes arrayed in rows of graded heights to form a crescent or W-shape on the apical surface of sensory hair cells. The stereocilia are deflected by the vibration of sound, which opens transduction channels and allows an influx of ions to depolarize the hair cell, in turn triggering synaptic activity. The specialized morphology and organization of the stereocilia bundle is crucial in the process of sensory transduction in the inner ear. However, we know little about the development of stereocilia in the mouse and few molecules that are involved in stereocilia maturation are known. We describe here a new mouse mutant with abnormal stereocilia development. The Tasmanian devil (tde) mouse mutation arose by insertional mutagenesis and has been mapped to the middle of chromosome 5. Homozygotes show head-tossing and circling and have raised thresholds for cochlear nerve responses to sound. The gross morphology of the inner ear was normal, but the stereocilia of cochlear and vestibular hair cells are abnormally thin, and they become progressively disorganized with increasing age. Ultimately, the hair cells die. This is the first report of a mutant showing thin stereocilia. The association of thin stereocilia with cochlear dysfunction emphasizes the critical role of stereocilia in auditory transduction, and the discovery of the Tasmanian devil mutant provides a resource for the identification of an essential molecule in hair cell function.
authors.affiliation: MRC Institute of Hearing Research, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Erven
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Skynner
authors.forename: Katsuzumi
authors.initials: K
authors.lastname: Okumura
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Takebayashi
authors.forename: Steve D M
authors.initials: SD
authors.lastname: Brown
authors.forename: Karen P
authors.initials: KP
authors.lastname: Steel
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Allen
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D002923:Cilia / Q000473:pathology* / Q000648:ultrastructure; D003056:Cochlear Nerve / Q000503:physiopathology; D003638:Deafness / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006198:Hair Cells, Auditory / Q000002:abnormalities* / Q000473:pathology / Q000648:ultrastructure; D006309:Hearing / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009154:Mutation / Q000235:genetics*; D009421:Nervous System Malformations / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D019076:Transgenes / Q000235:genetics