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.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Somatosensory and Chemosensory Systems Study Section (SCS)
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Davis, Barry
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Scripps Research Institute
La Jolla
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Stowers, Lisa; Liberles, Stephen D (2016) State-dependent responses to sex pheromones in mouse. Curr Opin Neurobiol 38:74-9
Stowers, Lisa; Kuo, Tsung-Han (2015) Mammalian pheromones: emerging properties and mechanisms of detection. Curr Opin Neurobiol 34:103-9
Dey, Sandeepa; Chamero, Pablo; Pru, James K et al. (2015) Cyclic Regulation of Sensory Perception by a Female Hormone Alters Behavior. Cell 161:1334-44
Kaur, Angeldeep W; Ackels, Tobias; Kuo, Tsung-Han et al. (2014) Murine pheromone proteins constitute a context-dependent combinatorial code governing multiple social behaviors. Cell 157:676-88
Stowers, Lisa; Cameron, Peter; Keller, Jason A (2013) Ominous odors: olfactory control of instinctive fear and aggression in mice. Curr Opin Neurobiol 23:339-45
Logan, Darren W; Brunet, Lisa J; Webb, William R et al. (2012) Learned recognition of maternal signature odors mediates the first suckling episode in mice. Curr Biol 22:1998-2007
Flanagan, Kelly A; Webb, William; Stowers, Lisa (2011) Analysis of male pheromones that accelerate female reproductive organ development. PLoS One 6:e16660
Stowers, Lisa; Logan, Darren W (2010) Olfactory mechanisms of stereotyped behavior: on the scent of specialized circuits. Curr Opin Neurobiol 20:274-80
Stowers, Lisa; Logan, Darren W (2010) Sexual dimorphism in olfactory signaling. Curr Opin Neurobiol 20:770-5
Papes, Fabio; Logan, Darren W; Stowers, Lisa (2010) The vomeronasal organ mediates interspecies defensive behaviors through detection of protein pheromone homologs. Cell 141:692-703

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