Characteristics of Pheromone Binding Proteins

信息素结合蛋白的特征

• 批准号: 7064776
• 负责人: LISA STOWERS
• 金额: $ 41.24万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7064776
• 关键词: aggression; animal communication behavior; behavior test; behavioral /social science research tag; binding proteins; biological models; biological signal transduction; embryonic stem cell; gene induction /repression; gene targeting; genetically modified animals; laboratory mouse; liver; mutant; pheromone; protein structure function; small molecule; social behavior; urine

DESCRIPTION (provided by applicant): Without the appropriate regulation of behavior such as aggression and mating, individuals cannot function in society. A growing number of Americans obtain therapeutic drugs to modify behavior, yet we have little understanding of the mechanisms and neuronal pathways that initiate behavioral responses. In mice, chemical cues called pheromones serve as signals between individuals to regulate their social behavior. Mouse pheromone response provides an experimentally approachable system to define the neuronal circuitry that regulates mammalian social behavior. The long-term goals of this proposal are to identify signals in the environment that influence behavior and their underlying molecular mechanisms. The mouse major urinary proteins (MUPs) family of genes displays characteristics consistent with a role in pheromone signaling. MUPs provide a molecular fingerprint of an individual's age, strain, and gender. MUPs display a hydrophobic binding pocket enabling them to be carrier proteins for pheromones. MUPs are expressed in secretory fluids with pheromone signaling activity and are excreted into the environment. Furthermore, MUPs co-purify with a bioactive fraction of urine that elicits social behavioral responses in mice. Based on these observations, the central hypothesis for the proposed research is that the MUPs are an integral component of pheromone signaling. To test this hypothesis the following specific aims are proposed: 1) Establish which MUPs are expressed in the liver, secreted into the urine, and transmitted between animals. 2) Define genetically the function of MUPs in pheromone signaling. 3) Define the function of liver specific MUPs in regulating social behavior. These aims will be tested using genomic and molecular genetic strategies to elucidate the extent to which MUPs function in pheromone signaling.

描述（由申请人提供）：如果没有适当的行为调节，例如侵略和交配，个人就无法在社会中发挥作用。越来越多的美国人获得治疗药物来改变行为，但是我们对启动行为反应的机制和神经元途径几乎没有理解。在小鼠中，称为信息素的化学提示是个体之间的信号，以调节其社会行为。小鼠信息素响应提供了一个实验上平易近人的系统，以定义调节哺乳动物社会行为的神经元电路。该提案的长期目标是确定影响行为及其潜在分子机制的环境中的信号。小鼠主要的尿蛋白（MUP）基因家族显示出与信息素信号传导中作用一致的特征。 MUP提供了个体年龄，压力和性别的分子指纹。 MUP显示一个疏水结合口袋，使它们成为信息素的载体蛋白。 MUP在具有信息素信号活性的分泌流体中表达，并排出环境。此外，MUP与尿液的生物活性分数共同绘制，从而引起小鼠的社会行为反应。基于这些观察结果，提出的研究的中心假设是MUP是信息素信号传导的组成部分。为了检验该假设，提出了以下特定目的：1）确定哪些MUP在肝脏中表达，分泌到尿液中，并在动物之间传播。 2）从遗传上定义了MUP在信息素信号传导中的功能。 3）定义特定MUP在调节社会行为中的功能。这些目标将使用基因组和分子遗传策略进行测试，以阐明MUPS在信息素信号中的功能的程度。