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: 2749272
• 负责人: DOUGLAS FORREST
• 金额: $ 24.91万
• 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/2749272
• 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 对于听觉系统的发育至关重要。 该提案将 关联听觉中的特定细胞和生理过程 具有从给定 TR 变体到确定的转录途径的开发 其下游靶基因来确定 TRa 和 TR 的程度 调解独特或不合作的功能。 听觉缺陷 TR缺陷小鼠将从形态和功能上进行研究， 重点关注耳蜗作为听觉中主要的 T3 敏感部位 系统。 这些研究旨在增强我们对角色的理解 T3 和 TR 基因在听觉发育和功能中的作用。 这些具体的 提案中列出的目标是：（1）研究细胞和 TR在耳蜗发育中的生理功能； (2) 调查 通过定向诱变研究TR 2在耳蜗中的功能和表达 TR 2 特异性外显子； (3) 确定个体和组合 TR和TRα的功能； (4) 研究配体的可用性 耳蜗发育； (5) 研究TR依赖的转录途径 （分离和表征目标基因）。