The winged helix transcription factor Fkh10 is required for normal development of the inner ear

• Published in: Nature genetics Vol. 20; no. 4; pp. 374 - 376
• Main Authors: Enerbäck, Sven, Hulander, Malin, Wurst, Wolfgang, Carlsson, Peter
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.12.1998
• Subjects: Acoustic Stimulation; Animals; Behavior, Animal; Biological and medical sciences; chromosome 5; Classical genetics, quantitative genetics, hybrids; Ear, Inner - embryology; Ear, Inner - physiopathology; Fkh10 gene; Fkh10 protein; FKHL10 gene; forkhead protein; Forkhead Transcription Factors; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Mice; Mice, Mutant Strains; Molecular Sequence Data; Nuclear Proteins - physiology; Transcription Factors - physiology; Vertebrata; Vestibular Diseases - genetics; Vestibular Diseases - physiopathology; vestibulum; Embryonic development; Animal model; Rodentia; Auditory disorder; Gene expression; Vestibule; Inner ear; Genetic disease; Hearing loss; Vertebrata; Mammalia; Gene; Mouse; Malformation; Cochlea; ENT disease; Mutation; Transcription factor
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/3850

Fkhl0 is a member of the forkhead family of winged helix transcriptional regulators. Genes encoding forkhead proteins are instrumental during embryogenesis in mammals, in particular during development of the nervous system. 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 vestibular dysfunction. These animals also fail to elicit a Preyer reflex in response to a suprathreshold auditory stimulation, as seen in mice with profound hearing impairment. Histological examination of the inner ear reveals a gross structural malformation of the vestibulum as well as the cochlea. These structures have been replaced by a single irregular cavity in which neither proper semicircular ducts nor cochlea can be identified. We also show that at 9.5 days post coitum (dpc), Fkh10 is exclusively expressed in the otic vesicle. These findings implicate Fkh10 as an early regulator necessary for development of both cochlea and vestibulum and identify its human homologue FKHL10 as a previously unknown candidate deafness gene at 5q34.