CORRECTION OF DEAFNESS IN SHAKER-2 MICE BY AN UNCONVENTIONAL MYOSIN IN A BAC TRANSGENE

The shaker-2 mouse mutation, the homolog of human DFNB3, causes deafne ss and circling behavior. A bacterial artificial chromosome (BAC) tran sgene from the shaker-2 critical region corrected the vestibular defec ts, deafness, and inner ear morphology of shaker-2 mice. An unconventi onal myosin gene, Myo15, was discovered by DNA sequencing of this BAG. Shaker-2 mice were found to have an amino acid substitution at a high ly conserved position within the motor domain of this myosin, Auditory hair cells of shaker-2 mice have very short stereocilia and a long ac tin-containing protrusion extending from their basal end. This histopa thology suggests that Myo15 is necessary for actin organization in the hair cells of the cochlea.