GENETIC ANALYSIS OF B3 ADRENERGIC RECEPTOR FUNCTION

B3 肾上腺素受体功能的遗传分析

• 批准号: 6517349
• 负责人: BRADFORD B LOWELL
• 金额: $ 39.21万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-30 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6517349
• 关键词: adipocytes; alpha adrenergic receptor; animal genetic material tag; beta adrenergic receptor; bioenergetics; dietary excess; genetically modified animals; genetics; human genetic material tag; laboratory mouse; mutant; nutrition related tag; obesity; protein structure function; receptor expression

Beta 3-adrenergic receptors (B3-AR) are thought to play an important role in regulating energy expenditure and B3-selective agonists are being developed as anti-obesity drugs. A number of unresolved issues persist regarding the potential of this receptor as an anti-obesity target. Knockout mice lacking B3-AR have been generated in the previous grant period. The present application proposed to 1) use mice lacking B3-ARs to assess the role of B3-ARs in regulating energy balance: influence of diet and background genes 2) to assess effects of genetically altered a2-AR/B3AR ratios or the Trp64Arg human B3-AR variant on adrenergic signalling in adipocytes; 3) to determine the molecular basis for selective expression of human B3-ARs in brown adipocytes; 4) to use mice lacking B3-AR to establish the existence of additional atypical B-ARs and to molecularly clone and characterize these novel receptors.

β3-肾上腺素能受体(B3-AR)被认为在 调节能量消耗的作用和B3选择性激动剂是 正在被开发为减肥药物。一些悬而未决的问题 坚持认为这种受体具有抗肥胖的潜力 目标。在之前的研究中已经产生了缺乏B3-AR的基因敲除小鼠 授权期。本申请建议1)使用缺乏 B3-ARs评估B3-ARs在调节能量平衡中的作用： 饮食和背景基因的影响2)评估治疗效果 基因改变的a2-AR/B3AR比率或Trp64Arg人B3-AR 脂肪细胞中肾上腺素能信号的变体；3)确定 人B3-ARs在棕色中选择性表达的分子基础 脂肪细胞；4)利用缺乏B3-AR的小鼠来证实 新的非典型B-ARs及其分子克隆和鉴定 这些新奇的受体。