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Effects on fear reactivity in XO mice are due to haploinsufficiency of a non-PAR X gene: implications for emotional function in Turner's syndrome

Isles, Anthony Roger, Davies, William, Burrmann, Doreen, Burgoyne, Paul S. and Wilkinson, Lawrence Stephen 2004. Effects on fear reactivity in XO mice are due to haploinsufficiency of a non-PAR X gene: implications for emotional function in Turner's syndrome. Human Molecular Genetics 13 (17) , pp. 1849-1855. 10.1093/hmg/ddh203

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Abstract

Recent work has indicated altered emotional functioning in Turner's syndrome (TS) subjects (45,XO). We examined the role of X-chromosome deficiency on fear reactivity in X-monosomic mice (39,XO), and found that they exhibited anxiogenic behaviour relative to normal females (40,XX). A molecular candidate for this effect is Steroid sulfatase (Sts) as this is located in the pseudoautosomal region (PAR) of the X-chromosome and consequently is normally biallelically expressed. In addition, the steroid sulfatase enzyme (STS) is putatively linked to fear reactivity by an effect on GABAA receptors via the action of neurosteroids. Real-time PCR demonstrated that levels of Sts mRNA were reduced by half in the brains of 39,XO mice compared with 40,XX, and that expression levels of a number of GABAA subunits previously shown to be important components of fear processing (Gabra3, Gabra1 and Gabrg2) were also altered. However, 40,XY*X mice, in which the Y*X is a small chromosome comprising of a complete PAR and a small non-PAR segment of the X-chromosome, exhibited the same pattern of fear reactivity behaviour as 39,XO animals, but equivalent expression levels of Sts, Gabra1, Gabra3 and Gabrg2 to 40,XX females. This showed that although Sts may cause alterations in GABAA subunit expression, these changes do not result in increased fear reactivity. This suggests an alternative X-chromosome gene, that escapes inactivation, is responsible for the differences in fear reactivity between 39,XO and 40,XX mice. These findings inform the TS data, and point to novel genetic mechanisms that may be of general significance to the neurobiology of fear.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Psychology
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Publisher: Oxford University Press
ISSN: 0964-6906
Last Modified: 24 Apr 2019 13:48
URI: http://orca.cf.ac.uk/id/eprint/621

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