Published online 5 December 2007 | Nature | doi:10.1038/news.2007.354


Pheromone for mouse aggression found

Study pins down protein mitt that makes mice fight.

One scent can get a mouse's back up.Getty

A whiff of a single type of protein from urine is enough to make a male mouse pick a fight, researchers have found. Pheromone scents that elicit aggressive behaviour have long been predicted, but have proven elusive until now.

Male mice will attack other mice they see as a threat, such as males that invade their territory, but will generally welcome females and leave juveniles or castrated males alone. When they do attack it can be quite aggressive. "The resident will chase the intruder, bite, kick and wrestle with him," says Lisa Stowers, a biologist at the Scripps Research Institution in La Jolla, California who along with her colleagues has identified a protein that provokes this aggression.

Stowers and her colleagues filtered mouse urine by fractionation to sort the molecules by size. They then tested to see which samples — when dabbed on a castrated male — elicited an aggressive response from resident males. The researchers narrowed the search down to a group of molecules called the major urinary proteins (MUPs), whose role in chemical communication has been only suspected until now.

MUPs form open ‘pockets’ like a baseball-catcher's glove, in which smaller molecules nestle. The MUPs were thought to be ‘catching’ the pheromones in these pockets. But the researchers found that it isn't the small molecules that have an effect on male mice. Displacing the cargo with a different small molecule didn't reduce the MUPs' ability to elicit aggression. And when the researchers digested away the protein mitt, leaving only the small molecules, the solution lost its effect.

So the protein alone works as an aggression pheromone, the team reports in Nature this week1. "It starts the whole behavioural response in motion," Stowers said.

The nose knows

Pheromones seem to be detected by a structure called the vomeronasal organ, a tube at the base of the nasal cavity directly behind the nostrils that is filled with sensory neurons (the main olfactory sensor is further back in the nose, and the two systems connect with separate parts of the brain).

When the researchers tagged vomeronasal organs with a fluorescent dye that makes receptors change colour when a molecule locks onto them, and spritzed on some MUPs, only one class of receptor responded. This helped to pin down the mechanism by which the scent is detected.


"It's very exciting if this is truly a pheromone that is specific to triggering aggressive behaviour," says Klaus Miczek who studies the brain chemistry underlying abnormal levels of aggression at Tufts University in Medford, Massachusetts. But he cautions that these MUPs might be more generally to do with social recognition rather than aggression specifically. Miczek says that he would like to see tests spraying female and juvenile intruders with MUPs as well.

Both Stowers and Miczek point out that because aggression in humans and mice depends on different triggers, such research probably won’t lead to treatments for abnormal levels of human violence. 

  • References

    1. Chamero P. et al., Nature doi:10.1038/nature05997
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