ANESTHETIC MECHANISMS IN GABA--R GENE TARGETED MICE

GABA-R 基因靶向小鼠的麻醉机制

• 批准号: 2519029
• 负责人: LEONARD L FIRESTONE
• 金额: $ 25.6万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2519029
• 关键词: GABA receptor; alleles; anesthetics; chloride channels; drug hypersensitivity; electrophysiology; gene targeting; general anesthesia; genetic strain; inhalation anesthesia; laboratory mouse; mutant; neurons; point mutation; protein isoforms; protein structure; tissue /cell culture

DESCRIPTION: (Adapted from the applicant's abstract) This study aims to elucidate the molecular target(s) of anesthetic action by creating knockout mice and examining the progeny for sensitivity to inhaled anesthetics. Six genetically altered mouse lines carrying mutations at GABAA receptor loci are proposed, specifically null alleles of a6, b3, g2, d subtypes, as well as point mutations of a6 and g2 subunits. These specific alleles have been chosen since inbred mice missing these alleles or carrying specific mutations have been shown previously to have altered sensitivity to anesthetic agents. After creation of the mouse strains, each will be tested for anesthetic sensitivity (5 volatile GAs on tail clamp/withdrawal MAC, loss of righting reflex), chloride flux experiments from brains of bred mice, and finally electrophysiologic studies to determine if single mutations change other neurons as well as characteristics of the channel with and without anesthetics. Hence behavioral and electrophysiology data are the endpoints of this project.

描述：（改编自申请人摘要）本研究旨在 为了阐明麻醉作用的分子靶点， 敲除小鼠和检查后代对吸入的敏感性， 麻醉剂六个基因改变的小鼠品系携带突变， 提出了GABAA受体基因座，特别是α 6，β 3， G2、D亚型，以及A6和G2亚基的点突变。这些 选择特定的等位基因，因为近交系小鼠缺少这些 等位基因或携带特定突变的基因， 改变了对麻醉剂的敏感性创建后， 小鼠品系，每种品系将测试麻醉剂敏感性（5 夹尾/撤回MAC时的挥发性GAs，翻正反射丧失）， 从繁殖小鼠的大脑中进行氯通量实验，最后 电生理学研究，以确定单个突变是否改变其他 神经元以及通道的特性， 麻醉剂因此，行为和电生理数据是 这个项目的终点。