Study Identifies Pheromones That Trigger Aggression Between Male Mice

Researchers have identified pheromones, which are responsible for the aggression response in mice.

The study, led by Lisa Stowers, PhD, has found a family of proteins commonly found in mouse urine, which is able to trigger fighting between male mice.

Pheromones are chemical cues that are released into the air, secreted from glands, or excreted in urine and picked up by animals of the same species, initiating various social and reproductive behaviours.

"Although the pheromones identified in this research are not produced by humans, the regions of the brain that are tied to behaviour 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 behaviour," Nature quoted James F. Battey, Jr., M.D., Ph.D., director of the NIDCD, which funded the study.

"Much is known about how pheromones work in the insect world, but we know very little about how these chemicals can influence behaviour in mammals and other vertebrates," he said.

Researchers at Scripps Research Institute, La Jolla, Calif., and Harvard University studied aggression because it is a strongly exhibited social behaviour in male mice.

In the study, the researchers narrowed the field of pheromone candidates by separating out progressively smaller compounds in the urine and studying their effects on both mouse behaviour and their ability to activate sensory receptor neurons in the vomeronasal organ.

The vomeronasal organ is one of two locations in the mouse's nasal cavity that houses sensory receptor cells that detect pheromones.

The scientists swabbed the backs of neutered male mice with the various pheromone candidates and placed them in a cage with a normal male mouse. Neutered males are useful for the study of aggression because they can neither emit nor detect the aggression pheromones. Whereas normal males will begin fighting as soon as they are placed together in a cage, neutered males remain docile around normal males, and vice versa.

If a neutered male whose back has been swabbed with a pheromone candidate elicits hostility in a normal male, the researchers know that the pheromone candidate is responsible for the behaviour.

Using a technique called calcium imaging, the team also studied whether pheromone candidates 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 colour when the neuron was activated.

The researchers discovered that the protein family that comprises the major urinary protein (MUP) complex in mouse urine is one of two pheromones that can elicit the aggression response in male mice.

"There are about 20 members of the MUP family, and each mouse expresses four to six of the members randomly. This creates a bar code of individuality for each mouse. And we don't know whether the proteins are actually coding for aggression per se, or whether they're serving as a general cue of individuality for a male,” Stowers said.

The study is published in Nature.

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