A genetic switch for gender bending

Female mice adopt male sexual behaviour including pelvic thrusts and mounting.

Female mice missing a gene involved in pheromone detection show the same sexual behaviour as males, researchers report this week (T. Kimchi et al. Nature doi:10.1038/nature06089; 2007).

The striking finding, by Catherine Dulac's group at Harvard University implies that female mice have a 'male behaviour' circuit in their brains, which can be activated by the flick of a single genetic switch.

Female mice genetically engineered to lack a gene called Trpc2 engaged in exclusively male traits, such as pelvic thrusting, male calls and mounting other mice, both female and male. The TRPC2 protein is essential for the functioning of the vomeronasal organ — a part of the mouse nose that is involved in sensing pheromones.

The results prompt a rethink about how the brain regulates sexual behaviour according to gender, but some query whether they could simply be an effect of the lab environment, or of the types of mice used.

Lab conditions, says Dulac, might cause mice to be more limited in their behaviour than they otherwise would be. So, her group tested the same mutant mice under more natural conditions, leaving them in a larger enclosure for a month. The Trpc2-knockout mice still behaved sexually as if they were males.

The genetic make-up of lab mice might also affect the results. There are three types of mouse, says geneticist Fernando Pardo-Manuel de Villena, of the University of North Carolina in Chapel Hill. There are the classical lab mice, descended from one original pool of pets, bred to be less aggressive than average; wild-derived lab strains, which are not bred on the basis of behaviour; and wild mice. Wild and lab mice are effectively chalk and cheese, with “strikingly different behaviour”, says Pardo-Manuel de Villena.

Dulac's group bred two of the most common classical lab mouse strains — the C57BL and the 129/Sv types — together, and used the offspring in their experiments. But wild mice may behave very differently, points out mouse geneticist Elissa Chesler, of Oak Ridge National Laboratory in Tennessee. “Would there be any compensation for this gene if this mutant was crossed to wild mice?”

Dulac's group is aware of this problem and is now breeding wild mice with the Trpc2-mutant mice, to experiment with a 'wilder' version.


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See News & Views, doi:10.1038/ nature05892

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Smith, K. A genetic switch for gender bending. Nature 448, 630–631 (2007). https://doi.org/10.1038/448630b

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