Two male mice often fight when put in a cage, but if one is neutered they get along fine. Decades ago, scientists found out that dabbing urine from an intact male mouse on the back of a neutered mouse gave the latter the chemical signature of an unaltered male. The neutered mouse soon found himself brawling with the guys.
Combining this behavioral test with modern biochemical analyses, molecular biologist Lisa Stowers and her colleagues at the Scripps Research Institute in La Jolla, Calif., now reveal some of the chemistry behind the aggression.
In male mouse urine, proteins in a cluster called the major urinary protein (MUP) complex function as pheromones that literally strike a nerve in other males, the scientists report in the Dec. 6 Nature. An individual mouse has only a few of the 20 or so proteins that can show up in an MUP cluster. In the study, those few were enough to act as a fight pheromone when researchers dabbed them on neutered males.
Because neutered mice don’t make significant amounts of testosterone, they lack MUP proteins, Stowers notes.
Pheromones are chemical cues given off by animals that trigger others’ behavior by binding to sensory receptors in the vomeronasal organ in mice.
To substantiate the behavioral findings, Stowers and colleagues placed the urine proteins in contact with live neurons obtained from male mouse vomeronasal organs in a lab dish. Using imaging techniques, the researchers detected when 1 of the roughly 250 receptors on the neurons was activated. The tests verified that the MUC proteins were pheromones and revealed that two neuron receptors, called Gnao and V2Rs, act as docking ports for them.