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.
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