A New Mutation of the Atoh1 Gene in Mice with Normal Life Span Allows Analysis of Inner Ear and Cerebellar Phenotype in Aging

Atoh1 is a transcription factor that regulates neural development in multiple tissues and is conserved among species. Prior mouse models of Atoh1 , though effective and important in the evolution of our understanding of the gene, have been limited by perinatal lethality. Here we describe a novel point mutation of Atoh1 (designated Atoh1 trhl ) underlying a phenotype of trembling gait and hearing loss. Histology revealed inner ear hair cell loss and cerebellar atrophy. Auditory Brainstem Response (ABR) and Distortion Product Otoacoustic Emission (DPOAE) showed functional abnormalities in the ear. Normal lifespan and fecundity of Atoh1 trhl mice provide a complementary model to facilitate elucidation of ATOH1 function in hearing,central nervous system and cancer biology.