Characteristics of Pheromone Binding Proteins

描述（由申请人提供）：如果没有适当的行为规范，如侵略和交配，个人不能在社会中发挥作用。越来越多的美国人获得治疗药物来改变行为，但我们对引发行为反应的机制和神经通路知之甚少。在老鼠身上，被称为信息素的化学信号作为个体之间的信号来调节它们的社会行为。小鼠信息素反应提供了一个实验上可接近的系统来定义调节哺乳动物社会行为的神经元回路。该提案的长期目标是确定环境中影响行为的信号及其潜在的分子机制。小鼠主要尿蛋白（MUP）基因家族显示出与信息素信号传导中的作用一致的特征。MUP提供了个体年龄、品系和性别的分子指纹。MUP显示疏水结合口袋，使它们能够成为信息素的载体蛋白。MUP在具有信息素信号传导活性的分泌液中表达并被排泄到环境中。此外，MUP与尿液的生物活性级分共纯化，其激发小鼠的社会行为反应。基于这些观察，所提出的研究的中心假设是，MUP是信息素信号的一个组成部分。为了检验这一假设，提出了以下具体目标：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)从遗传学上定义MUP在信息素信号传导中的功能。3)明确肝脏特异性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学策略进行测试，以阐明MUPs在信息素信号传导中的作用程度。

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.