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Mutant Mice Mate Rather Than Hate

31 January 2002 (All day)
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Mating games. Male mice lacking TRP2 don't know they should be fighting with each other.

A new genetically modified mouse that can't sniff out the sex of its partner will, to put it delicately, try to partner with it rather than attack it. That a single gene so markedly affects social interactions comes as a surprise to many researchers.

Mice detect smells in two ways. Most airborne smells trigger neurons that send messages to the brain's smell center, known as the primary olfactory cortex. But pheromones--a kind of personal identification molecule--stimulate a batch of 400 nerve cells in a part of the nose called the vomeronasal organ (VNO). The VNO sends signals to the hypothalamus, a brain region involved in reproduction, defense, and eating. On these VNO cells is a protein called TRP2 that's found nowhere else. Humans have remnants of the pheromone system, but unlike some other species aren't controlled by it.

To find out what this protein contributes to pheromone detection, a team led by Harvard molecular neuroscientist Catherine Dulac deleted the TRP2 gene. The group then bred mouse strains that had two, one, or no copies of the gene. All of the animals reproduced as if nothing were amiss. But when the researchers dropped an intruder mouse into an animal's cage, they saw some unusual behavior.

Normally, male mice attack other males but try to mate with females. But male mice with no copies of TRP2 tried to mate with either males or females. During these trysts, the males' VNO neurons were quiet, compared to the same neurons in normal mice. The researchers, whose work appears online at Science this week, conclude that TRP2 is necessary for detecting pheromones that indicate whether a strange mouse is a male.

The work is "superlative," says neurobiologist Emily Liman of the University of Southern California in Los Angeles. "It opens the way for genetic analysis of a plethora of behaviors," including sexual maturation, gender recognition, and spontaneous abortions in mice, all of which are influenced by pheromones.

Related sites
Catherine Dulac's home page
The vomeronasal organ
Background on olfaction

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