The accessory olfactory system in mice

描述（由申请人提供）：哺乳动物的嗅觉是由主嗅觉系统和副嗅觉（或犁鼻）系统介导的。传统观点认为，前者介导对“常见”气味的检测，而后者主要负责对信息素的识别。犁鼻系统的分子和生理途径尚未充分整合。在最近的工作中，Celera小鼠数据库被挖掘来表征小鼠V1R库的序列多样性。通过染色体工程技术，将包含2/12个V1R家族的16个V1R基因删除，获得了一个小鼠品系。雄性和雌性突变小鼠都表现出特定的行为缺陷，这为V1R基因和信息素相关行为之间提供了第一个联系。在人类基因组中已经鉴定出5个完整的v1r样受体基因。一种新的测定方法已经发展到测量犁鼻感觉神经元的生理反应。本文提出了一种综合方法来验证犁鼻受体负责检测信息素和其他社会重要分子的假设。目的1：表征由于染色体工程而缺乏各种犁鼻受体基因簇的突变小鼠株的表型。目的2：在小鼠神经元中功能表达人犁鼻受体。目的3：通过生物信息学表征小鼠V2R基因库，然后靶向删除选定的V2R基因簇。目的4：培养两种犁鼻感觉神经元中的一种被标记的小鼠品系，并从生理学上测试它们是否对应于双重化学感觉模式。两个实验室在犁鼻系统方面具有成熟和互补的专业知识，建议联合起来解决这些困难和突出的生物学问题。该结果将为哺乳动物信息素交流的生物学提供新的见解。

DESCRIPTION (provided by applicant): Olfaction is mediated in mammals by the main olfactory system and the accessory olfactory (or vomeronasal) systems. The traditional view is that the former mediates the detection of 'common' odorants, while the latter is primarily responsible for the recognition of pheromones. The molecular and physiologal approaches to the vomeronasal system have been insufficiently integrated. In recent work, the Celera mouse database was mined to characterize sequence diversity of the mouse V1R repertoire. A strain of mice was developed in which a cluster of 16 V1R genes, encompassing 2/12 V1R families, has been deleted by chromosome engineering. Both male and female mutant mice show specific behavioral deficits, providing the first link between V1R genes and pheromone-associated behaviors. Five intact V1R-like receptor genes have been identified in the human genome. A novel assay has been developed to measure physiological responses of vomeronasal sensory neurons. Here, a combined approach is proposed to test the hypothesis that vomeronasal receptors are responsible for the detection of pheromones and other socially important molecules. Aim 1: To characterize the phenotype of mutant mouse strains that lack various clusters of vomeronasal receptor genes as a result of chromosome engineering. Aim 2: To express human vomeronasal receptors functionally in neurons of mice. Aim 3: To characterize the mouse V2R repertoire by bioinformatics, followed by targeted deletions of selected V2R gene clusters. Aim 4: To develop mouse strains in which one of the two populations of vomeronasal sensory neurons is marked, and test physiologically if they correspond to dual chemosensory modalities. Two laboratories with proven and complementary expertise in the vomeronasal system propose to join forces to solve these difficult and outstanding biological issues. The results will provide new insights into the biology of pheromone communication in mammals.