NKX5-1 CONTROLS SEMICIRCULAR CANAL FORMATION IN THE MOUSE INNER-EAR

The inner ear develops from the otic vesicle, a one-cell-thick epithel ium, which eventually transforms into highly complex structures includ ing the sensory organs for balance (vestibulum) and hearing (cochlea), Several mouse inner ear mutations with hearing and balance defects ha ve been described but for most the underlying genes have not been iden tified, for example, the genes controlling the development of the vest ibular organs. Here, we report the inactivation of the homeobox gene, Nkx5-1, by homologous recombination in mice, This gene is expressed in vestibular structures throughout inner ear development, Mice carrying the Nkx5-1 null mutation exhibit behavioural abnormalities that resem ble the typical hyperactivity and circling movements of the shaker/wal tzer type mutants. The balance defect correlates with severe malformat ions of the vestibular organ in Nkx5-1(-/-)mutants, which fail to deve lop the semicircular canals, Nkx5-1 is the first ear-specific molecule identified to play a crucial role in the formation of the mammalian v estibular system.