Functional analysis of Trace Amine-Associated Receptors in vivo

描述（由申请人提供）：嗅觉，即嗅觉，对生活质量和整体人类健康有重要贡献。环境中的挥发性化学物质是由一大家族的气味受体检测到的，这是哺乳动物基因组中最大的基因库。气味受体家族包括三种不同类型的受体：I类和II类受体（包括超过1000个基因），以及最近发现的微量胺相关受体（TAARs）家族（14个基因）。这个小基因家族在包括人类在内的许多哺乳动物物种中都很保守，这表明TAARs在气味感知中具有独特而重要的作用。据推测，taar会对不稳定的社会线索做出反应。然而，这些受体的功能特性尚不清楚。本提案的目标是定义完整哺乳动物嗅觉系统中TAARs的功能特性，以验证这些受体特异性或优先响应气味剂（即胺）的假设。我将产生几个基因靶向小鼠品系，在这些品系中，嗅球中表达确定的TAAR基因的嗅觉感觉神经元及其相关的肾小球被荧光标记。然后，我将通过成像从遗传定义的肾小球气味诱发的活动来表征受体的反应概况。该实验将首次表征哺乳动物TAARs在体内的功能，并将作为确定这些受体如何影响哺乳动物气味感知的第一步。

DESCRIPTION (provided by applicant): Olfaction, the sense of smell, contributes significantly to quality of life and overall human health. Volatile chemicals in the environment are detected by a large family of odorant receptors, the largest repertoire of genes in the mammalian genome. The odorant receptor family comprises three phylogenetically distinct types of receptors: Class I and Class II receptors (comprising over 1000 genes), and a recently discovered family of Trace Amine-Associated Receptors or TAARs (14 genes). This small gene family is well-conserved in many mammalian species including humans, suggesting that TAARs have a unique and important role in odor perception. It has been speculated that the TAARs respond to volatile social cues. However, the functional properties of these receptors are poorly characterized. The goal of this proposal is to define the functional properties of TAARs in the intact mammalian olfactory system in order to test the hypothesis that these receptors respond specifically or preferentially to a subset of odorants (i.e. amines). I will generate several strains of gene-targeted mice in which the olfactory sensory neurons expressing defined TAAR genes and their associated glomeruli in the olfactory bulb are fluorescently labeled. I will then characterize the response profiles of the receptors by imaging odor-evoked activity from the genetically defined glomeruli. The proposed experiments will characterize for the first time the function of mammalian TAARs in vivo, and will serve as the first step in determining how these receptors contribute odor perception in mammals. PUBLIC HEALTH RELEVANCE: The sense of smell is critical for quality of life and overall human health. We are taking a novel approach to characterize how odorants are detected under normal conditions by a newly discovered class of olfactory receptors, the trace amine associated receptors. Our methods will allow us to characterize for the first time how molecular interactions at these receptors contribute to mammalian odor perception.