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Studies in cochlear hair cell transduction

耳蜗毛细胞转导研究

基本信息

批准号：
6874957
负责人：
PETER J DALLOS
金额：
$ 85.74万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-01-01 至 2006-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6874957
关键词：
biological signal transduction cochlea cochlear microphonic potentials ear hair cell electrophysiology gene expression gene targeting genetically modified animals hearing laboratory mouse membrane potentials protein structure function

项目摘要

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.

描述（改编自申请人的摘要）：在哺乳动物中，外毛细胞在负责耳朵声音的耳蜗中提供局部放大卓越的灵敏度和频率选择性。虽然依赖哺乳动物耳蜗基于局部、外毛细胞的放大被广泛已接受，但对于放大机制尚未达成一致。一种观点是在细胞受体电位的推动下，体细胞形状发生变化，称为电动性，提供机械反馈，从而放大。一个另一种概念是，扩增是作为细胞的附属物而出现的。向前的换能器过程，因此驻留在纤毛中。我们现在有鉴定出编码特殊运动蛋白（prestin）的基因产生电动势。因此，现在可以测试这些替代方案。我们将制作一个缺乏prestin（基因敲除小鼠）的小鼠模型并测试其听力。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 prestin无功能，听力已退化。此外，广泛对 prestin 本身的分子特性进行了实验目的是产生针对它的各种抗体，以确定其拓扑结构并它与已知影响外毛细胞的各种物质的相互作用动力。