The accessory olfactory system in mice

描述(申请人提供)：在哺乳动物中，嗅觉是由主嗅觉系统和副嗅觉(或犁鼻)系统调节的。传统观点认为，前者起到调节“普通”气味的作用，而后者主要负责信息素的识别。对犁鼻系统的分子和生理途径还没有充分整合。在最近的工作中，挖掘了Celera小鼠数据库以表征小鼠V1R谱系的序列多样性。通过染色体工程，培育出了一种小鼠，其中包含2/12个V1R家族的16个V1R基因簇已经被删除。雄性和雌性突变小鼠都表现出特定的行为缺陷，这提供了V1R基因和信息素相关行为之间的第一个联系。已在人类基因组中鉴定出5个完整的V1R样受体基因。一种新的检测方法已经被开发出来用于测量犁鼻感觉神经元的生理反应。在这里，提出了一种组合的方法来检验这样的假设，即犁鼻受体负责检测信息素和其他重要的社会分子。目的1：研究由于染色体工程而导致犁鼻受体基因簇缺失的突变小鼠的表型特征。目的2：在小鼠神经元中表达人犁鼻受体。目的3：利用生物信息学方法对小鼠V2R基因谱系进行鉴定，并对选定的V2R基因簇进行靶向缺失。目的：建立具有两种犁鼻感觉神经元之一的小鼠品系，并对它们是否符合双重化学感觉模式进行生理学测试。两个在犁鼻系统方面拥有公认和互补专业知识的实验室提议联手解决这些困难和悬而未决的生物学问题。这一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.