Understanding the function of trace amine-associated (TAARs)

描述（由申请人提供）：在哺乳动物中，气味是由排列在鼻子嗅上皮（OE）上的嗅觉感觉神经元（OSNs）检测到的。osn表达嗅觉受体，这是一种专门检测气味的G蛋白偶联受体。在小鼠中有大约1000个OR基因，在人类中有大约350个。大量的嗅觉嗅觉和气味剂对这些嗅觉嗅觉的组合激活使得对无数气味嗅觉的辨别成为可能。然而，最近，我们的实验室在小鼠OE中发现了第二个由14个化学感觉受体组成的家族。编码这些受体的基因，称为微量胺相关受体（TAARs），存在于小鼠、人类和鱼类中，并且在鱼类和小鼠OE中都有发现。与ORs一样，单个小鼠TAARs在仅表达该受体的osn的独特亚群中表达。筛选不同气味剂的TAARs发现了几种TAARs的配体，这些TAARs都是小挥发性胺。有趣的是，至少有三种小鼠TAARs识别尿液中的胺。其中一种检测到与压力有关的化合物，而另外两种检测到男性和女性尿液中富含的化合物。TAAR家族的进化保守表明，该家族可能具有不同于ORs的化学感觉功能。到目前为止，为TAARs识别的配体暗示了一种与社会线索检测相关的功能。在本研究中，我们将进一步研究TAARs在小鼠中的作用。首先，我们将使用钙成像技术来检测组织培养细胞中表达的个体TAARs对不同性别、年龄、生殖状态、应激水平和遗传背景的小鼠分泌物的反应。接下来，我们将使用放射性TAAR探针来标记OSN轴突中的mrna，研究嗅球中TAAR信号是如何组织的。最后，我们将测试我们鉴定的TAAR配体是否可以刺激小鼠的生理作用。

DESCRIPTION (provided by applicant): In mammals, odorants are detected by olfactory sensory neurons (OSNs) that line the olfactory epithelium (OE) of the nose. OSNs express olfactory receptors, which are G protein-coupled receptors specialized in detecting odors. There are ~1000 OR genes in mice, and ~350 in humans. The large numbers of ORs and the combinatorial activation of those ORs by odorants allow for discrimination of myriad odorants. Recently, however, our lab has found a second family of fourteen chemosensory receptors in the mouse OE. Genes encoding these receptors, called trace amine-associated receptors (TAARs) are present in mouse, human, and fish, and are found in both the fish and mouse OE. Like ORs, individual mouse TAARs is expressed in unique subsets of OSNs that express only that receptor. Screening of TAARs with diverse odorants revealed ligands for several TAARs, all of which are small volatile amines. Interestingly, at least three mouse TAARs recognize amines found in urine. One detects a compound linked to stress while the other two detect compounds enriched in male versus female urine. The evolutionary conservation of the TAAR family suggests that this family may have a chemosensory function distinct from ORs. Ligands identified for TAARs thus far hint at a function associated with the detection of social cues. In the proposed studies, we will further investigate the roles played by TAARs in the mouse. First, we will use calcium imaging to test individual TAARs expressed in tissue culture cells for responses to mouse secretions obtained from mice of different sex, age, reproductive status, stress levels, and genetic background. Next, we will examine how TAAR signals are organized in the olfactory bulb using radioactive TAAR probes to label mRNAs in OSN axons. Finally, we will test whether TAAR ligands we have identified can stimulate physiological effects in mice.