Pheromones control sex discriminati...( tudies on in vitro preparations of VN...)

tudies on in vitro preparations of VNO tissue from the knockout mice. Meister and Holy applied mouse urine -- known to contain a mix of pheromones -- to VNO tissue and used multi-electrode arrays to measure the electrical activity of the VNO tissue. The studies confirmed that the VNO from the knockout mice did not respond properly to pheromone signals. Additional physiological studies of the knockout mice revealed that the wiring of their VNOs appeared normal, ruling out a developmental defect as the reason why mating behavior persisted in the knockout mice.

After the scientists established that mice with otherwise normal VNOs could not respond to pheromones, lead author Lisa Stowers, an HHMI research associate, began to study the behavioral effects of knocking out TRP2. In one experiment, Stowers painted the backs of male mice with urine and introduced them into the cages of knockout mice. The knockout mice failed to show aggression toward their new cage mates.

"It is well known that if you put a male mouse in a cage for a while, it establishes the cage as its territory; and if you put another male in the cage, it will be attacked," said Dulac. "And this attack relies on detection of pheromones by the resident male.

"Besides this lack of aggression by the knockout mice, Lisa Stowers observed another very strange thing -- the knockout males tried to mate with the intruder males," said Dulac. "It took us a while to realize what that might mean," she said. "We theorized that the knockout male could be hyper-sexed -- willing to mate with any animal -- or it might not be able to detect the difference."

The scientists solved the puzzle when they placed the knockout mice in cages with either males or females and found that the knockout mice attempted to mate with either sex. Additional studies showed that the knockout mice emitted the same mating-related ultrasound vocalizations with males and females, demonstrating that a ful
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
31-Jan-2002

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