Function of hair cells regenerated by Atoh1

Atoh1再生毛细胞的功能

• 批准号: 7156968
• 负责人: MARK A CRUMLING
• 金额: $ 3.44万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7156968
• 关键词: Actins; Amplifiers; Animals; Area; Biological; Cavia; Cell physiology; Cells; Cellular Structures; Characteristics; Cytokeratin; Ear; Electric Capacitance; Fellowship; Gene Delivery; Generations; Genes; Hair; Hair Cells; Hearing Impaired Persons; Individual; Inner Hair Cells; Labyrinth; Life; Measurement; Mediating; Membrane; Molecular; Morphology; Motor; Myosin ATPase; Names; Natural regeneration; Organ of Corti; Outer Hair Cells; Phenotype; Physiological; Property; Proteins; Recovery; Research; Supporting Cell; TRPA1 Channel; Techniques; Testing; Viral; Work; gene therapy; in vivo; otoacoustic emission; partial recovery; patch clamp; rat Pres protein; reconstruction; research study; restoration; voltage

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.

描述（由申请人提供）：病毒介导的Atohl基因向耳毒性中毒豚鼠的内耳的递送导致Corti器官中新毛细胞的产生和ABR阈值的恢复（Izumikawa等人，2005年）。为了进一步重建失聪耳朵中正常功能的Corti器官，有必要对Atohl基因治疗后出现的细胞进行表征。内毛细胞区再生的毛细胞形态正常，ABR阈值恢复表明传入功能恢复。然而，在外毛细胞区域再生的毛细胞似乎具有毛细胞和支持细胞之间的混合表型。这些细胞对恢复阈值的贡献是未知的，因为它们在多大程度上获得了外毛细胞的分子和功能特征。这项研究的工作假设是，在前外毛细胞领域再生的毛细胞获得功能性外毛细胞表型。这是使用分子生物学，电生理学和听力学技术来探测内耳外毛细胞结构和功能的标志。