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Pheromone sensing in mammals

哺乳动物的信息素感应

基本信息

批准号：
6999754
负责人：
TRESE LEINDERS-ZUFALL
金额：
$ 32.99万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-04-01 至 2007-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6999754
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

项目摘要

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，特别是那些潜在的复杂社会行为，如攻击、母性照顾和交配。大多数哺乳动物的化学感觉是通过至少两种不同的鼻腔组织实现的：主嗅上皮（MOE）和犁鼻器官（VNO）。在过去的两年里，人们对VNO在嗅觉交流和信息素感知中的作用进行了大量的研究，但一个关键的问题仍然存在：vsn中信号转导机制的本质是什么？本应用程序的目标1就是围绕这个问题展开的。与此同时，越来越多的证据表明，在哺乳动物中，上颌部的感觉神经元也可能对信息素的交流至关重要。这些细胞的身份及其信号机制尚不清楚。目标2解决了这个问题。我们的主要目标是通过确定VNO和MOE中信息素感知的细胞和分子机制来缩小我们知识中的这些关键空白。为了达到这一目标，我们将在Aim 1中重点关注VSNs中信息素转导的一个重要组成部分，即瞬时受体电位（TRP）通道TRPC2。该应用程序的主要目的是利用TRPC2基因靶向缺失的独特敲除小鼠，了解TRPC2形成通道的激活和调控机制。TRP通道基因家族的成员最近被认为是多种感官系统的重要组成部分，包括味觉、加热和平衡的感觉。因此，我们的研究结果对于更好地理解不同感觉模式的编码和转导策略具有普遍意义。在Aim 2中，我们将重点关注MOE中一个神秘的感觉神经元亚群的功能，即GC-D细胞，它表达膜guany酰环化酶GC-D和其他几种蛋白质，使人想起cgmp依赖的转导途径。我们将首次系统分析GC-D细胞的生理特性，包括它们对化学感觉配体的反应，利用基因靶向小鼠破坏编码GC-D的基因，并用报告基因特异性标记GC-D细胞。具体来说，我们将测试GC-D细胞系统作为信息素检测系统的假设，这是检测有限的一组生物相关化学信号所必需的。