The accessory olfactory system in mice

哺乳动物的嗅觉由主嗅觉系统和副嗅觉系统介导 (or犁鼻）系统。传统的观点认为，前者介导了 “普通”气味，而后者主要负责识别信息素。的 犁鼻系统的分子和生理学方法还不够 整合在最近的工作中，Celera小鼠数据库被挖掘以表征序列 小鼠VIR库的多样性。开发了一种小鼠品系，其中16个VIR的簇 基因，包括2/12的VIR家族，已被删除的染色体工程。男性 而雌性突变小鼠表现出特定的行为缺陷，提供了VIR之间的第一个联系。 基因和信息素相关行为。五个完整的VIR样受体基因已经被 在人类基因组中被发现。已经开发了一种新的测定方法来测量生理 犁鼻感觉神经元的反应。 在这里，提出了一种组合的方法来检验犁鼻受体的假设， 负责检测信息素和其他重要的社会分子。 目的1：描述缺乏犁鼻器不同簇的突变小鼠品系的表型 受体基因作为染色体工程的结果。 目的2：在小鼠神经元中表达人犁鼻受体。 目的3：通过生物信息学表征小鼠V2 R库，然后选择靶向缺失 V2 R基因簇。 目的4：建立犁鼻感觉神经元的两个群体之一是 标记，并在生理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 提议联合起来解决这些困难和悬而未决的生物问题。结果将 为哺乳动物信息素交流的生物学提供了新的见解。

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 VIR repertoire. A strain of mice was developed in which a cluster of 16 VIR genes, encompassing 2/12 VIR families, has been deleted by chromosome engineering. Both male and female mutant mice show specific behavioral deficits, providing the first link between VIR genes and pheromone-associated behaviors. Five intact VIR-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 qf 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.