Rockefeller Researchers Provide The First Functional Evidence For Mammalian Pheromone Receptors

In the Sept. 5 issue of the journal Nature, Mombaerts and colleagues at Rockefeller, University of Maryland School of Medicine and Monell Chemical Senses Center report significantly less aggressive and sexual behavior in laboratory mice who were engineered to lack a particular cluster of genes that previous research from the Rockefeller lab had linked to pheromone detection. They also show that the nerve cells of mutant mice are unable to detect certain pheromones. These pheromone receptors are found in the lining of the animals' vomeronasal organ (VNO), a part of the olfactory system thought to be specialized in the detection of pheromones.

"We know that the VNO is involved with pheromones because if it is surgically removed from the animals, several abnormalities in their mating behavior and aggression patterns arise," says Karina Del Punta, the lead author on this paper and a graduate student at The Rockefeller University.

"We found that deleting the cluster of genes that produce pheromone receptors replicates some aspects of the surgical removal of the VNO in these animals."

The researchers used a sophisticated technique of genetic manipulation called "chromosome engineering technology" to delete a region of 16 genes from the genome of the mouse. The mutant mice developed normally, were fertile and were indistinguishable from normal or control animals with respect to their general behavior.

However, the mutant males and females displayed clear differences in aggression and sexual activity compared to their normal counterparts.

Normally, nursing females are aggressive toward other lab mice that intrude or invade their nest. The nursing mutant females, however, were less aggressive when confronted by an intruder: there were fewer attacks, the first attack was delayed, and the total time spent attacking the invader was much less, when compared to the behavior of the females' normal counterparts in the same test situation.

The researchers studied four behaviors in the male mutant mice, and found two of these to be affected in the mutant mice. A first assay tested if male mutants emit 70 kilohertz ultrasounds when first exposed to a female. Removing the VNO reduces this behavior, but in the mutant mice it was unaltered. Second, male aggression against other males was also unchanged in the mutants.

A third test focused on male-male sexual behavior. Socially inexperienced mice are often observed to exhibit sexual behaviors toward other males until they become more experienced and learn to distinguish males from females. Socially inexperienced mutant mice, surprisingly, made fewer sexual advances toward males, suggesting that the mutants are better at distinguishing between sexes without prior experience, or that their sexual drive overall is reduced.

The fourth behavioral test analyzed sexual behavior of males toward females,