Abstract
Whilst gonadal hormones can substantially influence sexual differentiation of the brain, recent findings have suggested that sex-linked genes may also directly influence neurodevelopment. Here we used the well-established murine ‘four core genotype’ (FCG) model on a gonadally-intact, outbred genetic background to characterise the contribution of Sry-dependent effects (i.e. those arising from the expression of the Y-linked Sry gene in the brain, or from hormonal sequelae of gonadal Sry expression) and direct effects of sex-linked genes other than Sry (‘sex chromosome complement’ effects) to sexually dimorphic mouse behavioural phenotypes. Over a 24 hour period, XX and XY gonadally female mice (lacking Sry) exhibited greater horizontal locomotor activity and reduced food consumption per unit bodyweight than XX and XY gonadally male mice (possessing Sry); in two behavioural tests (the elevated plus and zero mazes) XX and XY gonadally female mice showed evidence for increased anxiety-related behaviours relative to XX and XY gonadally male mice. Exploratory correlational analyses indicated that these Sry-dependent effects could not be simply explained by brain expression of the gene, nor by circulating testosterone levels. We also noted a sex chromosome complement effect on food (but not water) consumption whereby XY mice consumed more over a 24hr period than XX mice, and a sex chromosome complement effect in a third test of anxiety-related behaviour, the light-dark box. The present data suggest that: i) the male-specific factor Sry may influence activity and feeding behaviours in mice, and ii) dissociable feeding and anxiety-related murine phenotypes may be differentially modulated by Sry and by other sex-linked genes. Our results may have relevance for understanding the molecular underpinnings of sexually dimorphic behavioural phenotypes in healthy men and women, and in individuals with abnormal sex chromosome constitutions.
Highlights
Across mammalian species males and females typically differ with respect to key aspects of physiology and behaviour
On a further measure of anxiety, time spent in the protected closed arms, there was a significant main effect of SRY DEPENDENCE whereby gonadally male mice spent less time in these zones than gonadally female mice (F1,83=5.269, p
The four core genotypes (FCG) mouse model permits a dissociation to be made between neurobiological effects that are due to the influence of the Y chromosome-encoded Sry protein, and effects that arise due to the actions of sex-linked genes other than Sry
Summary
Across mammalian species males and females typically differ with respect to key aspects of physiology and behaviour. Whilst there is fairly consistent data regarding the direction of effects for the first two measures (whereby males consume more food and achieve higher bodyweights [11,12], and females are more active [13,14]), the data regarding the direction of anxiety-related behaviours is more uncertain [15,16]. This uncertainty could reflect inter-study heterogeneity related to the strain and species used, differences in experimental protocols, or failure to account for stage of female oestrus [17]
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