Delving into the minds of men and women can be a profitable enterprise, as the authors of best-sellers such as Men Are from Mars, Women Are from Venus would no doubt testify. Neuroscientists have also taken a keen interest in male–female differences — or dimorphisms — in the brain, but usually to answer more fundamental scientific questions than why men leave the lavatory seat up, or why women take so long to get dressed. In the Journal of Neuroscience, De Vries et al. report on a new transgenic mouse model for studying the genetic basis of sexual dimorphism.

Sexual dimorphism in the brain can take many forms, from variations in the sizes of various structures to differences in behaviour. Sex hormones exert a strong influence on the brain, both during development and throughout life, so it has been assumed that most masculine or feminine brain characteristics are acquired secondary to testis or ovary development. However, De Vries et al. proposed that there might be genes on the sex chromosomes that affect the brain directly, so they created a mouse model that would help them to identify these factors.

Testis development depends on a single gene on the Y chromosome — the Sry gene. In the absence of Sry, ovaries develop by default. The authors generated a transgenic mouse line in which Sry was moved from the Y chromosome to an autosome. By performing various intercrosses between these and wild-type mice, they obtained XY 'females' (designated XY−), XX 'males' (XXSry), and XY males with Sry on an autosome instead of the Y chromosome (XY−Sry). They compared XXSry males with XY−Sry animals rather than wild-type males, to control for the possibility that Sry functions differently in the context of an autosome.

Consistent with previous findings, the authors found that most structural and behavioural dimorphisms were determined by whether the mouse had testes or ovaries. However, when they compared the density of vasopressin-immunoreactive (VP-ir) fibres in the brains of their mice, they made an intriguing discovery. Normally, males have a higher density of VP-ir fibres in the septum than females, and the XY−Sry mice had a higher density of fibres than XXSry mice, even though the XXSry mice had testes. Similarly, the XY− mice had a higher density of fibres than normal XX mice, even though both had ovaries. These findings indicate that this characteristic is influenced by factors other than Sry on the sex chromosomes.

De Vries et al. speculate that three types of gene could be responsible for non-hormonally induced sexual dimorphisms — genes on the Y chromosome, X-linked genes that escape X-inactivation, and X-linked genes whose activity is modified by maternal or paternal imprinting. The influence of the sex chromosomes on behaviour has important sociological as well as scientific implications; for example, men with an extra copy of the Y chromosome show a tendency towards aggressive and criminal behaviour. Is this simply the result of too much testosterone, or would an extra copy of the Y chromosome minus the Sry gene have a similar effect on behaviour? The new mouse model provides a powerful means of addressing this and other important questions about sexually dimorphic traits.