THE WINGED HELIX TRANSCRIPTION FACTOR FKH10 IS REQUIRED FOR NORMAL DEVELOPMENT OF THE INNER-EAR

Fkh10 is a member of the forkhead family of winged helix transcription al regulators. Genes encoding forkhead proteins are instrumental durin g embryogenesis in mammals, in particular during development of the ne rvous system(1-5). Here we report that mice with a targeted disruption of the Fkh10 locus exhibit circling behaviour, poor swimming ability and abnormal reaching response-all common findings in mice with vestib ular dysfunction(6). These animals also fail to elicit a Preyer reflex in response to a suprathreshold auditory stimulation, as seen in mice with profound hearing impairment(7,8). Histological examination of th e inner ear reveals a gross structural malformation of the vestibulum as well as the cochlea. These structures have been replaced by a singl e irregular cavity in which neither proper semicircular ducts nor coch lea can be identified. We also show that at 9.5 days post coitum (dpc) , Fkh10 is exclusively expressed in the otic vesicle. These findings i mplicate Fkh10 as an early regulator necessary for development of both cochlea and vestibulum and identify its human homologue FKHL10 as a p reviously unknown candidate deafness gene at 5q34.