THYROID HORMONE RECEPTORS AND GENETIC CONTROL OF HEARING

甲状腺激素受体和听力的遗传控制

• 批准号: 6379399
• 负责人: DOUGLAS FORREST
• 金额: $ 27.22万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6379399
• 关键词: animal genetic material tag; behavioral /social science research tag; cochlea; developmental genetics; genetically modified animals; hearing; hormone receptor; laboratory mouse; neurogenetics; organ culture; protein structure function; receptor expression; thyroid hormones

DESCRIPTION: Thyroid hormone (T3) and its two receptors (TRa and TR ) are essential for the development of the auditory system. This proposal will correlate specific cellular and physiological processes in auditory development with defined transcriptional pathways from a given TR variant to its downstream target genes to determine the extent to which TRa and TR mediate unique or uncooperative functions. The auditory defect in TR-deficient mice will be investigated morphologically and functionally, focusing on the cochlea as the primary T3-sensitive site in the auditory system. These studies are designed to enhance our understanding of the role of T3 and TR genes in auditory development and function. These specific aims as listed in the proposal are: (1) To investigate the cellular and physiological functions of TR in cochlear development; (2) To investigate the function and expression of TR 2 in the cochlea by targeted mutagenesis of a TR 2-specific exon; (3) To determine the individual and combined functions of TR and TR[alpha]; (4) To investigate ligand availability in the developing cochlea; (5) To investigate TR-dependent transcriptional pathways (to isolate and characterize target genes).

描述：甲状腺激素（T3）及其两种受体（TRa和TR）是 对听觉系统的发育至关重要。 这项建议会 将听觉中特定的细胞和生理过程联系起来， 从给定的TR变体到具有确定的转录途径的发展 其下游靶基因，以确定TRa和TR 介导独特的或不合作的功能。 听觉缺陷 将对TR缺陷小鼠进行形态学和功能研究， 将耳蜗作为听觉系统中的主要T3敏感部位 系统 这些研究旨在加强我们对 T3和TR基因在听觉发育和功能中的作用。 这些具体 本研究的主要目的是：（1）研究细胞和细胞外基质， TR在耳蜗发育中的生理功能;（2）探讨TR在耳蜗发育中的作用 TR 2基因在耳蜗中的功能和表达 TR 2特异性外显子;（3）确定单个和组合的 TR和TR[alpha]的功能;（4）研究配体在 （5）研究TR依赖的转录途径 (to分离和表征靶基因）。