Analysis of sex chromosome effects on behaviour

• Main Author: Lynn, Phoebe Mei Ying
• Published: Cardiff University 2011
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.585207

Sexual dimorphisms are seen in healthy individuals and in disorders. Recent research in model systems has challenged the dogma that sexual dimorphisms in the brain arise solely from sex differences in gonadal hormones such studies have suggested that products encoded by sex- linked genes may act direcdy on the brain, interacting with or independently of gonadal hormones, to contribute to aspects of neural sexual dimorphism. In this thesis, two mouse models were used to determine the extent to which gonadal hormones and sex-linked genetic mechanisms underpinned aspects of behaviour. The first of these models, the XO mouse, enables us to identify brain processes influenced by X-monosomy (i.e. lack of an X chromosome), or X-linked genomic imprinting (i.e. the parental origin of the single X chromosome). The second of these models, the Four Core Genotypes (FCG) cross allows a dissociation between brain and behavioural effects due to the action of the Y-linked gene Sry (either direct brain effects, or indirect effects on gonadal hormone secretion) and of other sex-linked genes. Data from the XO mouse model suggested an X-monosomy effect on the acquisition of two biconditional discriminations, but no effects on response conflict, as measured by a novel murine version of the 'Stroop task' the X-monosomy effect was not due to non-specific effects on physiology or behaviour. Data from the second model suggested XYY-dependent effects on anxiety (as indexed by the elevated zero maze) and on initial acquisition of a stimulus-reinforcer contingency in a two-way visual discrimination paradigm, but not on reversal learning. Assays of systemic testosterone levels and Sry brain expression in FCG mice and wildtype males indicated that the anxiety phenotype may be primarily due to testosterone, whilst the acquisition effect was more likely to be due to Sry expression in the brain. These data highlight the importance of direct effects of sex-linked genes on brain and behaviour. They may be of relevance to understanding the mechanisms underlying neuropsychological abnormalities in disorders, such as Turner syndrome (X-monosomy) and XYY, and sexual differentiation of the brain in mammals.