ANESTHETIC MECHANISMS IN GABA--R GENE TARGETED MICE

GABA-R 基因靶向小鼠的麻醉机制

• 批准号: 2190901
• 负责人: LEONARD L FIRESTONE
• 金额: $ 12.36万
• 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/2190901
• 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：(摘自申请者的摘要)本研究的目的 通过创造阐明麻醉作用的分子靶点(S) 基因敲除小鼠并检查其后代对吸入的敏感性 麻醉剂。六个携带突变基因的转基因小鼠品系 GABAA受体基因座被提出，特别是a6，b3， G_2、D亚型以及A_6和G_2亚基的点突变。这些 由于近交系小鼠缺少特定的等位基因，因此已经选择了这些等位基因 等位基因或携带特定突变之前已经被证明 已经改变了对麻醉剂的敏感性。在创建了 小鼠品系，每个品系都将接受麻醉敏感性测试(5 尾夹/后退MAC上的挥发性气体，恢复反射丧失)， 培育小鼠大脑的氯离子通量实验，最后 电生理学研究以确定单个突变是否会改变其他 神经元以及有无经络的特点 麻醉剂。因此，行为和电生理数据是 此项目的终结点。