title: Tailchaser (Tlc): a new mouse mutation affecting hair bundle differentiation and hair cell survival.
abstract: We have undertaken a phenotypic approach in the mouse to identifying molecules involved in inner ear function by N-ethyl-N-nitrosourea mutagenesis followed by screening for new dominant mutations affecting hearing or balance. The pathology and genetic mapping of the first of these new mutants, tailchaser (Tlc), is described here. Tlc/+ mutants display classic behavioural symptoms of a vestibular dysfunction, including head-shaking and circling. Behavioural testing of ageing mice revealed a gradual deterioration of both hearing and balance function, indicating that the pathology caused by the Tlc mutation is progressive, similar to many dominant nonsyndromic deafnesses in humans. Based on scanning electron microscopy (SEM) studies, Tlc clearly plays a developmental role in the hair cells of the cochlea since the stereocilia bundles fail to form the characteristic V-shape pattern around the time of birth. By young adult stages, Tlc/+ outer hair bundles are grossly disorganised although inner hair bundles appear relatively normal by SEM. Increased compound action potential thresholds revealed that the Tlc/+ cochlear hair cells were not functioning normally in young adults. Similar to inner hair cells, the hair bundles of the vestibular hair cells also do not appear grossly disordered. However, all types of hair cells in the Tlc/+ inner ear eventually degenerate, apparently regardless of the degree of organisation of their hair bundles. We have mapped the Tlc mutation to a 12 cM region of chromosome 2, between D2Mit164 and D2Mit423. Based on the mode of inheritance and map location, Tlc appears to be a novel mouse mutation affecting both hair cell survival and stereocilia bundle development.
authors.affiliation: MRC Institute of Hearing Research, University Park, Nottingham NG7 2RD, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Kiernan
authors.forename: M
authors.initials: M
authors.lastname: Zalzman
authors.forename: H
authors.initials: H
authors.lastname: Fuchs
authors.forename: M
authors.initials: M
authors.lastname: Hrabe de Angelis
authors.forename: R
authors.initials: R
authors.lastname: Balling
authors.forename: K P
authors.initials: KP
authors.lastname: Steel
authors.forename: K B
authors.initials: KB
authors.lastname: Avraham
mesh_terms: D000818:Animals; D001309:Auditory Threshold; D001522:Behavior, Animal; D002454:Cell Differentiation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D002874:Chromosome Mapping; D002923:Cilia / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D003051:Cochlea / Q000473:pathology / Q000648:ultrastructure; D005799:Genes, Dominant; D006198:Hair Cells, Auditory / Q000473:pathology* / Q000648:ultrastructure; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000235:genetics*; D008855:Microscopy, Electron, Scanning; D009154:Mutation; D010037:Otolithic Membrane / Q000166:cytology; D015837:Vestibular Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology