UNRAVELING THE GENETICS OF DEAFNESS

Hearing-impaired mouse mutants not only are good models for human here ditary deafness, but also are extremely useful for understanding the m olecular basis of the cochlear defect. We describe here how we identif ied the gene responsible for the deafness and vestibular defects in th e shaker-1 mouse mutant as a myosin VII gene. Three different mutation s, all causing the same phenotype in different lines of mouse, were fo und, providing good evidence that we had, indeed, found the correct ge ne. The same gene was subsequently found to be involved in Usher's syn drome type 1B, which features deafness, vestibular dysfunction, and pr ogressive retinitis pigmentosa. The myosin VII gene is expressed in se nsory hair cells, but not in supporting cells or neurons. We are inves tigating the role of myosin VII in hair cell development and function. Analysis of the different mutant stocks suggests it has at least two functions. First, it is involved in the development and maintenance of the stereocilia bundle. Second, it has a role in inner hair cell func tion. No evidence of retinal degeneration like that in Usher's syndrom e has been found in the shaker-1 mutants so far studied. The benefits of understanding the function of the gene for families with Usher's ty pe 1B are discussed. This gene is the first to be identified as causin g the most common type of disorder in human hearing impairment, neuroe pithelial abnormalities, and suggests a new class of candidate genes f or involvement in such defects.