Functional analysis of Trace Amine-Associated Receptors in vivo

描述（由申请人提供）：嗅觉，嗅觉，对生活质量和整体人类健康有显着贡献。环境中的挥发性化学物质是由一个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遗传学上不同类型的受体：I类和II类受体（包含超过1000个基因），以及最近发现的痕量胺相关受体或TAAR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非常保守，这表明TAAR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的特点很差。 该提案的目标是定义TAAR在完整的哺乳动物嗅觉系统中的功能特性，以测试这些受体特异性或优先响应于气味剂（即胺）的子集的假设。我将产生几个品系的基因靶向小鼠，其中表达确定的TAAR基因的嗅觉感觉神经元和它们在嗅球中的相关肾小球被荧光标记。然后，我将通过对遗传定义的肾小球的气味诱发活动进行成像来表征受体的反应概况。拟议的实验将首次表征哺乳动物TAAR在体内的功能，并将作为确定这些受体如何促进哺乳动物气味感知的第一步。 公共卫生相关性：嗅觉对生活质量和整体人类健康至关重要。我们正在采取一种新的方法来表征气味是如何在正常条件下检测到一类新发现的嗅觉受体，痕量胺相关受体。我们的方法将使我们能够首次表征这些受体的分子相互作用如何影响哺乳动物的气味感知。

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.