Making a butch mouse

ScientificAmerican.com August 05, 2007 Inside Every Girl Mouse Brain Is a Swaggering Boy Mouse—And It Doesn't Take Much to Bring Him Out All it takes is a little genetic manipulation or brain surgery to make female mice act like pelvic thrusting, rump-sniffing, aggressive males Female lab mice tend to be docile, passive creatures. But by either genetically shutting down or surgically removing their ability to smell pheromones, scientists transformed them into aggressive, pelvic-thrusting, vocalizing lotharios—without any significant rise in testosterone or other steroid hormones. "The female brain has the neuronal circuit both to control male and female behavior," says molecular neuroscientist Catherine Dulac of Harvard University. "What is sexually dimorphic is the switch that allows one to be silenced." The key to gender-specific behavior, in mice at least, is a cluster of receptors in their noses that allows them to smell pheromones, special chemicals that deliver information about sexual readiness, among other things, between members of the same species. Called the vomeronasal organ (VNO), it connects to the brain and registers the gender of other mice, triggering the appropriate response. But when the researchers genetically disabled the VNO, female mice began to chase their male peers, mount them and attempt to pelvic thrust [see video here ]. "From a behavioral standpoint you could not recognize the animal from being any different than the male," Dulac adds. "All the thinking until now was that female brains can produce feminine behaviors while male brains can produce masculine behaviors, with little or no cross talk between them," says Marc Breedlove, a neuroscientist at Michigan State University in East Lansing. "These results do suggest that, at least for mice, the brain retains circuitry to display both masculine and feminine behaviors into adulthood." Surgically removing the VNO also provoked the same behavior, the researchers report online in Nature. The full range of male mouse behaviors were on offer: from pelvic thrusting to high-pitched songs designed to woo mates. "Females never do this—ultrasound vocalizations," Dulac notes. "People thought that they didn't have the larynx." Although the females acted macho at times, they also retained the biological functions of their gender, ultimately becoming pregnant when paired with males (though only after aggressively trying to mount said males). Their maternal instinct was not as strong, however, as they wandered off from their pups after a few days, unlike normal mouse mothers. It remains unclear if disabling the VNO in males would make them act like females, because female lab mice are largely passive and do not exhibit any particularly distinct behaviors, Dulac says. But it is very clear female and male mouse brains are functionally identical. "It's easier to do it that way," Dulac adds. "If you have to imagine how to build two entirely different circuits, it's complicated." It also remains unclear how broadly the finding may apply. Fruit flies display similar behavior, but additional studies will be needed to assess the wider effect. "For other animals, we need to explore whether the VNO has this same dramatic effect," Breedlove says. "Is this true for all rodents? What about carnivores?" As for humans, we appear to lack VNOs and pheromones may play a less critical role in our mating rituals. "Humans are relying much more on visual cues," Dulac notes. But our brains may be wired similarly with "both circuits present and one is constantly inhibited." The key to gender-specific behaviors may have less to do with hormones and more to do with how various neural circuitry gets triggered.