Function of hair cells regenerated by Atoh1

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DESCRIPTION (provided by applicant): Viral mediated delivery of the Atohl gene to the inner ear of ototoxically deafened guinea pigs results in the generation of new hair cells in the organ of Corti and recovery of ABR thresholds (Izumikawa et al., 2005). To further the reconstruction of a normally functioning organ of Corti in deaf ears, it is necessary to characterize the cells that appear after Atohl gene therapy. Hair cells regenerated in the inner hair cell area appear to have normal morphology, and ABR threshold recovery suggests a restoration of afferent function. The hair cells regenerated in the outer hair cell area, however, appear to have a phenotype mixed between that of a hair cell and that of a supporting cell. The contribution of these cells to the recovery of thresholds is unknown, as is the extent to which they have acquired the molecular and functional characteristics of outer hair cells. The proposed research operates under the working hypothesis that hair cells regenerated in the former outer hair cell field acquire a functional outer hair cell phenotype. This is accomplished using molecular biological, electrophysiological, and audiological techniques to probe the inner ear for hallmarks of outer hair cell structure and function.