Pheromones Trigger Aggression Between Male Mice

A family of proteins commonly found in mouse urine can spark a fight between male mice, researchers have found. The finding is a major step in understanding how chemical cues called pheromones communicate messages between mammals.

Pheromones are released into the air, secreted from glands or excreted in urine and sensed by other animals of the same species, cuing various social and reproductive behaviors. Scientists understand a great deal about how pheromones work in the insect world, but little about how they influence behavior in mammals.

Researchers at Scripps Research Institute and Harvard University, funded in part by NIH's National Institute on Deafness and Other Communication Disorders (NIDCD), set out to study the role of pheromones in male mouse aggression, a social behavior that's relatively easy to track. Mouse urine had previously been linked to aggressive behavior in males, and earlier research by the group showed that this response depends on receptor neurons in the mouse's nasal cavity, in an area called the vomeronasal organ. This organ and the main olfactory epithelium, also in the nasal cavity, both contain sensory receptor cells able to detect pheromones.

As they reported in the December 6, 2007, issue of Nature, the researchers first narrowed the field of pheromone candidates by separating compounds in urine by size. They studied the effects of the chemical fractions on mouse behavior by swabbing the fractions on the backs of neutered male mice. They then placed a swabbed mouse in a cage with a normal one. Neutered males and normal males typically remain docile around each other. If a neutered male whose back has been swabbed triggers hostility in a normal male, the researchers know that the compounds are responsible.

The scientists also tested whether the fractions were able to directly activate sensory receptor neurons. Receptor neurons were removed from a mouse vomeronasal organ, spread out on a Petri dish and labeled with a substance that changed color when the neuron was activated.

The researchers found that 2 fractions contained pheromones. They purified one of them further and discovered that the major urinary protein (MUP) complex is responsible for the aggression response. They also found that the MUP protein is recognized exclusively in the vomeronasal organ, not in the main olfactory epithelium, and activates a specific type of sensory receptor neuron.

NIDCD Director Dr. James F. Battey, Jr. said, "Although the pheromones identified in this research are not produced by humans, the regions of the brain that are tied to behavior are the same for mice and people. Consequently, this research may one day contribute to our understanding of the neural pathways that play a role in human behavior."

The team now plans to explore how these signals are sifted and processed by the brain. Further research will also examine the still-unknown pheromone in the other fraction.