Studies in cochlear hair cell transduction

描述（改编自申请人摘要）：哺乳动物的外毛细胞 在耳蜗中提供局部放大， 灵敏度高，频率选择性好。虽然依赖于 哺乳动物耳蜗局部，外毛细胞为基础的基础上广泛扩增 接受，但没有关于放大机制的协议。一种观点认为 在细胞受体电位的驱动下， 电动性提供机械反馈，从而放大。一个 另一个概念是，扩增作为细胞的一种辅助手段而出现。 前向换能器过程，因此驻留在硬纤毛中。我们现在已经 确定了编码专门的运动蛋白（普雷斯廷）的基因， 产生电动性。因此，现在可以测试这些替代方案。 我们将产生一个缺乏普雷斯廷的小鼠模型（敲除小鼠），并测试其 听证会正常的听力意味着第二种放大机制 是有效的，而严重的听力损失将表明，由于 无功能性普雷斯廷，听力下降。此外，广泛 对普雷斯廷本身的分子性质进行实验， 目的是生产各种抗体，以确定其拓扑结构， 其与已知影响外毛细胞的各种试剂的相互作用 能动性

DESCRIPTION (Adapted from applicant's abstract): In mammals, outer hair cells provide local amplification in the cochlea that is responsible for the ear's remarkable sensitivity and frequency selectivity. While the reliance of the mammalian cochlea on local, outer hair cell based-based amplification is widely accepted, there is no agreement about the amplifying mechanism. One view is that, powered by the cell's receptor potential, somatic shape changes, called electromotility, provide mechanical feedback and thereby amplification. An alternative concept is that amplification arises as an adjunct to the cell's forward transducer process and thus resides in the sterocilia. We have now identified the gene that codes for the specialized motor protein (prestin) that produces electromotility. Thus, it is now possible to test these alternatives. We shall produce a mouse-model that lacks prestin (knockout mouse) and test its hearing. Normal hearing will imply that the second mechanism of amplification is operative, whereas significant hearing loss will show that due to the non-functional prestin, hearing has been degraded. In addition, extensive experiments are conducted on the molecular properties of prestin itself with aims of producing various antibodies against it, to determine its topology and its interaction with various agents that are known to influence outer hair cell motility.