Tailchaser (Tlc): A new mouse mutation affecting hair bundle differentiation and hair cell survival

We have undertaken a phenotypic approach in the mouse to identifying molecu les involved in inner ear function by N-ethyl-N-nitrosourea mutagenesis fol lowed by screening for new dominant mutations affecting hearing or balance. The pathology and genetic mapping of the first of these new mutants, tailc haser (Tlc), is described here. Tlc/+ mutants display classic behavioural s ymptoms of a vestibular dysfunction, including head-shaking and circling. B ehavioural testing of ageing mice revealed a gradual deterioration of both hearing and balance function, indicating that the pathology caused by the T lc mutation is progressive, similar to many dominant nonsyndromic deafnesse s in humans. Based on scanning electron microscopy (SEM) studies, Tlc clear ly plays a developmental role in the hair cells of the cochlea since the st ereocilia bundles fail to form the characteristic V-shape pattern around th e time of birth. By young adult stages, Tlc/+ outer hair bundles are grossl y disorganised although inner hair bundles appear relatively normal by SEM. Increased compound action potential thresholds revealed that the Tlc/+ coc hlear 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/+ i nner ear eventually degenerate, apparently regardless of the degree of orga nisation 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 aff ecting both hair cell survival and stereocilia bundle development.