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Sex drive and aggression linked to pheromone receptor genes in mice



Scientists have pinpointed a cluster of genes that mice need to detect pheromones, the chemical signals used to modulate sexual and reproductive behavior. The genes encode protein receptors involved in perceiving pheromones. Mice born without the receptors have clear deficits: Males have a diminished sex drive and females are less aggressive in defending their nests.

Diagram of the mouse V1r repertoire. Dashed lines enclose V1ra and V1rb families.

Karina Del Punta, of The Rockefeller University in New York, and colleagues used a technique called chromosome engineering to delete 16 pheromone receptor genes on mouse chromosome 6. The receptors are part of a superfamily of genes called V1r, which includes about 140 genes. Peter Mombaerts, also of Rockefeller, led the study.

Researchers have previously characterized V1r genes, but the new study is the first to demonstrate their role in detecting pheromones. The mutant mice behave abnormally and are unable to perceive some pheromonal molecules, according to findings published in Nature.

Much of what is known about pheromones and behavior has come from studies of mice that no longer have the organ that detects pheromones, the vomeronasal organ, or VNO. This organ is located in the nasal cavity and can be removed by surgery.

In the new study, the male mutant mice had a lower sex drive than normal males. They initiated fewer sexual encounters, but otherwise developed normally and were fertile. For males that did mount a female, their level of sexual activity compared similarly to that of normal mice.

Nursing mothers that lacked V1r genes were far less aggressive in defending their nest area against invaders than normal mothers. In other respects, however, the females seemed normal. They spent the usual amount of time retrieving their pups, for instance.

To investigate the cause of this aberrant behavior, the researchers tested the vomeronasal organ. They detected no electrophysiological response to three of eight pheromonal molecules in the VNOs of mutant mice. The loss of receptors was the reason for this, the researchers concluded.

The loss of a subset of V1r genes may 'corrupt' pheromone coding rather than blocking it, the researchers say, and this may affect mice in ways that are different than the complete surgical removal of the VNO. They speculate that the loss of a single Vr gene may be sufficient to affect behavior.

Earlier this year, researchers reported in Science that deleting the mouse channel protein TRP2 (for Transient Receptor Protein) caused males to attempt to mate with other males. Usually, male mice are territorial and become aggressive around other males.

The study concluded that a major function of the vomeronasal system is to provide the brain with necessary cues that help males select females as mates. The researchers reinforced the smell of male mice by splashing them with urine, which contains pheromones, but the mutant males were apparently unable to detect the signals.

See related GNN articles
»Scents and Pheromones
»Survivor in the human genome: Proposed human pheromone receptor is expressed in olfactory tissue

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Del Punta, K. et al. Deficient pheromone responses in mice lacking a cluster of vomeronasal receptor genes. Nature 419, 70-74 (September 5, 2002).
Leypold, B.G. et al. Altered sexual and social behaviors in trp2 mutant mice. Proc Natl Acad Sci USA 99, 6376-6381 (April 30, 2002).
Stowers, L. et al. Loss of sex discrimination and male-male aggression in mice deficient for TRP2. Science 295, 1493-1500 (February 22, 2002).

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