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: 6043398
• 负责人: DOUGLAS FORREST
• 金额: $ 25.66万
• 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/6043398
• 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).

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来说是必不可少的。这项提议将 听觉中特定的细胞和生理过程相互关联 从给定的tr变异体到给定的tr变异体的特定转录途径的发育 它的下游靶基因决定了tra和tr的程度 调解独特的或不合作的功能。儿童的听力缺陷 将从形态和功能上对TR1缺陷小鼠进行研究， 集中在耳蜗处，作为听觉中主要的T3敏感部位 系统。这些研究旨在加强我们对这一角色的理解 T_3和T_R基因在听觉发育和功能中的作用。这些特定的 提案中列出的目标是：(1)调查细胞和 受体在耳蜗体发育中的生理作用；(2)探讨 靶向诱变技术研究TR2在耳蜗组织中的功能和表达 TR2特异性外显子；(3)确定个体和组合 Tr和tr[α]的功能；(4)研究配体在 (5)研究tr依赖的转录途径。 (以分离和鉴定目的基因)。