Dissociable effects of Sry and sex chromosome complement on activity, feeding and anxiety-related behaviours in mice - PubMed (original) (raw)

Eleni Kopsida et al. PLoS One. 2013.

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. Anxiety-related and activity measures on the elevated plus maze.

The four groups of mice from the FCG cross spent equal time in the open arms of the elevated plus maze (A), and made equivalent numbers of entries into these zones (B). Gonadally female mice spent significantly longer time in the relatively unaversive closed arms than gonadally male mice irrespective of karyotype (C, *p<0.05), but all four groups made equal numbers of entries into these zones (D).

Figure 2

Figure 2. Anxiety-related and activity measures in the open field test.

All four experimental groups from the FCG cross spent an equal amount of time in the aversive central portion of the arena (A), made equal numbers of entries into this area (B), and showed equal latencies in making the first entry into this zone (C). There was a significant interaction between SRY DEPENDENCE and SEX CHROMOSOME COMPLEMENT on activity within the open field, consistent with gonadally female mice with an XX karyotype being more active than gonadally female mice with an XY karyotype, and gonadally male mice with an XY karyotype being more active than gonadally male mice with an XX karyotype (D).

Figure 3

Figure 3. Anxiety-related, activity and exploratory measures in the light-dark box test.

Mice with an XY karyotype spent a greater proportion of time in the dark compartment of the apparatus than mice with an XX karyotype, irrespective of gonadal type (A, *p<0.05). The four experimental groups displayed equivalent numbers of transitions between the two boxes (B). Gonadally male mice tended to take longer than gonadally female mice to enter the aversive light box (C) irrespective of karyotype (*p<0.05). The four experimental groups demonstrated equivalent degrees of exploratory behaviour as indexed by rearing (D).

Figure 4

Figure 4. Anxiety-related and activity measures in the elevated zero maze.

Gonadally female mice spent significantly less time than gonadally male mice on the aversive open quadrants of the elevated zero maze irrespective of karyotype (A, *p=0.05), and made fewer entries into these zones (B, *p<0.05).

Figure 5

Figure 5. Measures of activity, shelter time and food consumption over a 24hr continuous monitoring period.

Gonadally female mice were more active than gonadally male mice irrespective of karyotype, as indexed by horizontal activity (A) but there was no difference between the four experimental groups on a second measure of activity, number of running wheel revolutions (B). All four groups spent equal amounts of time in the shelter (C). Gonadally male mice, and mice with an XY karyotype, consumed more food per unit bodyweight than gonadally female mice (*p<0.05) and mice with an XX karyotype (D).

Figure 6

Figure 6. Brain Sry expression levels (A) and serum testosterone levels (B) in gonadally male FCG mice.

There was no significant difference in brain Sry expression between male FCG mice and whilst mean serum testosterone levels were higher in XY-Sry mice than XX_Sry_ mice, this difference was not statistically significant.

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