Functional Expression of Human Trace Amine-Associated Receptors in Mice

小鼠中人类微量胺相关受体的功能表达

• 批准号: 8706124
• 负责人: Thomas Bozza
• 金额: $ 19.31万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8706124
• 关键词: Afferent Neurons; Amines; Brain; Cell Culture System; Cells; Chemicals; Cilia; Coupled; Cues; Data; Dorsal; Electrophysiology (science); Environment; Family; Food; Future; Gene Targeting; Generations; Genes; Genetic; Goals; Health; Human; Label; Laboratories; Ligands; Light; Mammals; Measures; Mediating; Methods; Molecular; Mouse Strains; Mus; Odorant Receptors; Odors; Olfactory Epithelium; Olfactory Pathways; Orphan; Pheromone; Physiological; Population; Preparation; Property; Quality of life; Receptor Gene; Signal Transduction; Smell Perception; Source; Specificity; System; Time; Tissues; Vertebrates; cell type; chemical release; in vivo; member; microbial; olfactory bulb; olfactory receptor; optical imaging; patch clamp; public health relevance; receptor; receptor function; research study; response; social; tool

DESCRIPTION (provided by applicant): Human olfaction provides a unique window into understanding normal brain function. Odorous chemicals in the environment are detected by a large family of canonical odorant receptors, and a much smaller family of Trace Amine-Associated Receptors (TAARs). There are only 6 intact TAARs in humans and the TAARs are conserved in many vertebrate species, suggesting a common, important function. However, very little is known about the functional properties of human TAARs due to the limitations of current methods to express odorant receptors in cell culture systems. Here we propose to circumvent these issues by functionally expressing all of the human TAARs in mouse olfactory sensory neurons in vivo. Specific Aim 1 is to generate a set of gene-targeted mouse strains in which each of the human TAARs is expressed in a defined population of fluorescently labeled olfactory sensory neurons. Specific Aim 2 is to functionally characterize human TAARs by recording electrophysiological responses from TAAR-expressing olfactory sensory neurons in these mice. These studies should allow us to identify for the first time ligands for the human TAARs, and should shed light on how the TAAR genes contribute to human olfaction.

描述（由申请人提供）：人类嗅觉为理解正常的大脑功能提供了独特的窗口。环境中有气味的化学物质是由大型的规范气味受体家族检测到的，而痕量胺相关的受体（TAARS）的家族较小。人类只有6个完整的TAAR，而TAAR在许多脊椎动物中都保守了，这表明具有共同的重要功能。 但是，由于当前表达细胞培养系统中气味受体的局限性，人们对人TAAR的功能特性知之甚少。 在这里，我们建议通过功能表达体内嗅觉感觉神经元中的所有人类TAAR来避免这些问题。 具体目的1是生成一组基因靶向的小鼠菌株，其中每个人类TAAR都在定义的荧光标记的嗅觉感觉神经元中表达。 具体目标2是通过记录这些小鼠中表达TAAR嗅觉神经元的电生理反应来表征人类TAAR的表征。 这些研究应该使我们能够首次识别人类TAAR的配体，并应阐明TAAR基因对人类嗅觉的贡献。