Using mouse models to investigate sex-linked genetic effects on brain, behaviour and vulnerability to neuropsychiatric disorders.

Many brain and behavioural phenotypes in humans exhibit some degree of sexual dimorphism. Moreover, there are large and replicable differences in the vulnerability of the two sexes to a wide range of common brain disorders. Ultimately, sex differences in healthy individuals, or in pathological states, must arise as a consequence of the differential complement of sex-linked genes in males and females. These genes may act indirectly (for example through influencing gonadal hormone secretion), or directly, to influence brain development and function. In this review, I discuss how genetically tractable mouse models may be employed to inform our knowledge of the molecular basis of sexual differentiation of the mammalian brain, and how such models may therefore represent a useful tool through which to identify risk factors predisposing to sex-biased neuropsychiatric disorders.