Function of hair cells regenerated by Atoh1

描述(申请人提供)：病毒介导的Atohl基因进入耳毒性耳聋豚鼠的内耳，导致Corti器官中新的毛细胞的产生和ABR阈值的恢复(Izumikawa等人，2005年)。为了进一步重建耳聋患者正常功能的Corti器官，有必要对Atohl基因治疗后出现的细胞进行鉴定。内毛细胞区再生的毛细胞形态正常，ABR阈值恢复提示传入功能恢复。然而，在外毛细胞区再生的毛细胞似乎具有介于毛细胞和支持细胞之间的表型。这些细胞对阈值恢复的贡献尚不清楚，它们在多大程度上获得了外毛细胞的分子和功能特征也是未知的。这项拟议的研究是在一个工作假设下进行的，即在以前的外毛细胞场中再生的毛细胞获得了功能正常的外毛细胞表型。这是利用分子生物学、电生理学和听力学技术来探测内耳的外毛细胞结构和功能的特征。

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.