Pheromone sensing in mammals

哺乳动物的信息素感应

• 批准号: 6778999
• 负责人: TRESE LEINDERS-ZUFALL
• 金额: $ 33.78万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6778999
• 关键词: aggression; animal communication behavior; biological signal transduction; diacylglycerols; ethology; gene targeting; genetically modified animals; laboratory mouse; membrane channels; olfactions; pheromone; respiratory epithelium; sex behavior; social behavior; vomeronasal systems

DESCRIPTION (provided by applicant): This application is for renewal of research directed toward understanding the molecular and cellular events that mediate olfactory communication in mice, specifically those events underlying complex social behaviors such as aggression, maternal care, and mating. Chemosensation in most mammals is achieved by at least two distinct nasal tissues: the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). The past two years have seen an explosion of studies aimed at understanding the role of the VNO in olfactory communication and pheromone sensing, but a key question remains: What is the nature of the signal transduction mechanism in vomeronasal sensory neurons (VSNs)? Aim 1 of this application is centered on this question. At the same time, evidence is accumulating that sensory neurons in the MOE may also be crucial for pheromone communication in mammals. The identity of the cells and their signaling mechanisms are obscure. Aim 2 addresses this problem. Our main goal is to narrow these critical gaps in our knowledge by determining the cellular and molecular mechanisms that underlie pheromone sensing in the VNO and MOE. To reach this goal we will focus in Aim 1 on an essential component of pheromone transduction in VSNs, the transient receptor potential (TRP) channel TRPC2. A major aim of this application will be to understand the mechanisms underlying activation and regulation of the channels formed by TRPC2, taking advantage of a unique knockout mouse with a targeted deletion in the TRPC2 gene. Members of the TRP channel gene family have recently emerged as essential components in a variety of sensory systems including the senses of taste, heating and balance. Therefore, our results should be of general interest for a better understanding of coding and transduction strategies across different sensory modalities. In Aim 2, we will focus on the function of an enigmatic subpopulation of sensory neurons in the MOE known as GC-D cells, which express the membrane guanylyl cyclase GC-D and several other proteins reminiscent of a cGMP-dependent transduction pathway. We will provide the first systematic analysis of the physiological properties of GC-D cells, including their responses to chemosensory ligands, taking advantage of gene targeted mice that both disrupt the gene that encodes GC-D and specifically label the GC-D cells with a reporter. Specifically, we will test the hypothesis that the GC-D cell system functions as a pheromone detection system necessary for the detection of a limited set of biologically relevant chemical signals.

描述（由申请人提供）：本申请旨在更新研究，旨在了解介导小鼠嗅觉交流的分子和细胞事件，特别是那些复杂社会行为（如攻击、母性护理和交配）的事件。在大多数哺乳动物中，化学感觉通过至少两种不同的鼻组织实现：主嗅上皮（莫伊）和犁鼻器（VNO）。在过去的两年里，已经看到了爆炸性的研究，旨在了解的作用，VNO在嗅觉通信和信息素感知，但一个关键的问题仍然存在：犁鼻感觉神经元（VSNs）的信号转导机制的性质是什么？本申请的目的1集中在这个问题上。与此同时，越来越多的证据表明，莫伊中的感觉神经元也可能对哺乳动物的信息素通信至关重要。这些细胞的身份及其信号传导机制尚不清楚。目标2解决了这个问题。我们的主要目标是通过确定VNO和莫伊中信息素感测的细胞和分子机制来缩小我们知识中的这些关键差距。为了实现这一目标，我们将集中在目标1上的信息素转导的VSN，瞬时受体电位（TRP）通道TRPC 2的一个重要组成部分。本申请的一个主要目的将是了解TRPC 2形成的通道的激活和调节的潜在机制，利用在TRPC 2基因中具有靶向缺失的独特敲除小鼠。TRP通道基因家族的成员最近已经成为各种感觉系统的重要组成部分，包括味觉，加热和平衡感。因此，我们的研究结果应该是一个更好地了解不同的感觉方式的编码和转导策略的普遍兴趣。在目标2中，我们将重点关注莫伊中感觉神经元的神秘亚群的功能，称为GC-D细胞，其表达膜鸟苷酸环化酶GC-D和其他几种蛋白质，使人联想到cGMP依赖的转导途径。我们将提供GC-D细胞的生理特性的第一个系统分析，包括它们对化学感受配体的反应，利用基因靶向小鼠，既破坏编码GC-D的基因，又用报告基因特异性标记GC-D细胞。具体来说，我们将测试的假设，GC-D细胞系统的功能作为一个信息素检测系统所需的一组有限的生物相关的化学信号的检测。