Human beings tend to avoid places that smell of urine. But to mice, there is something positively addictive about the scent; they like to go back to a spot where they found the excretions again and again. Now, researchers have discovered that this behavior is triggered by a single protein in the urine of male mice.
Mice use scent to mark their territory, advertise their social dominance, and convey information about their health and reproductive status. But these are usually volatile pheromones that disperse quickly, and it has remained unclear what exactly stimulates a female to be attracted to a specific male.
Previous research had shown that female laboratory mice often return to a place where they have come across cage bedding soiled by males. Now, researchers at the University of Liverpool in the United Kingdom have confirmed this. Female mice spent five times as much time in a place where they had encountered a dish with male urine than at a place where they encountered water. Just 10 minutes of exposure to the urine was enough for the mice to show this place preference even after 14 days.
However, if the mice were prevented from touching the urine with their nose by a mesh screen, the place seemed to lose its attractiveness. "That suggested that the story was not as simple as everybody assumed and volatile pheromones were not responsible," says behavioral ecologist Jane Hurst, one of the authors of the study. By separating the urine into different fractions, the scientists showed that a protein called darcin that they had identified in 2005—and which mice can only detect if their noses touch the urine—is responsible for the frequent visits. Pure darcin, produced in cell culture in the lab, elicited the same reaction, the authors report online today in Science.
"This is a really compelling story," says Lisa Stowers, a neuroscientist at the Scripps Research Institute in San Diego, California. "Mammals were thought to be much more complex, but this study shows that a single chemical can lead [them to act] in a certain way." The study is "very simple and elegant," she adds. But it also raises new questions. For instance: There are many other ways a mouse could learn to return to a certain place. "So what is the benefit of evolving this [special] mechanism?"
Hurst says that what fascinates her is that the pheromones induce learning in the mice. And the animals do not only learn to be attracted to the place where they encountered the darcin. "They learn the odor cues of that specific male and are then attracted to it," Hurst says. "Being familiar with a scent really seems to be important for whether a female is interested in a male." The reason, Hurst suggests, is that dominant males, who make attractive mates, tend to leave the most marks in a certain territory.
The researchers showed that male mice, too, are attracted to a place if they have encountered darcin there, probably to foster a behavior called countermarking. "If males come across another male's scent mark, they put their own, fresher urine there," Hurst explains. This could also be the reason why some laboratory strains seem to have lost the ability to produce darcin: Because laboratory mice are usually group-housed, they have been selected to be less aggressive, and not producing darcin could help reduce tensions.