Elsevier

Biological Psychiatry

Volume 61, Issue 12, 15 June 2007, Pages 1351-1360
Biological Psychiatry

Original Article
X-Monosomy Effects on Visuospatial Attention in Mice: A Candidate Gene and Implications for Turner Syndrome and Attention Deficit Hyperactivity Disorder

https://doi.org/10.1016/j.biopsych.2006.08.011Get rights and content

Background

The loss of all, or part of an X chromosome, in Turner syndrome (TS, 45,XO) results in deficits in attentional functioning.

Methods

Using a 39,XO mouse model, we tested the hypothesis that X-monosomy and/or parental origin of the single X chromosome may influence visuospatial attentional functioning in a 5-choice serial reaction time task (5-CSRTT).

Results

Under attentionally demanding conditions 39,XO mice displayed impaired discriminative response accuracy and slowed correct reaction times relative to 40,XX mice; these deficits were alleviated in a version of the task with reduced attentional demands. Parental origin of the X did not affect performance of the 5-CSRTT. In contrast, the attentional phenotype was rescued in 40,XY*X mice possessing a single maternally inherited X chromosome and a small Y*X chromosome that comprises a complete pseudoautosomal region (PAR), and a small X-specific segment.

Conclusions

Our findings are consistent with an X-monosomy effect on attention and suggest the existence of X-linked gene(s) that escape X-inactivation, are present on the small Y*X chromosome and impact on attentional functioning; the strongest candidate gene is Sts, encoding steroid sulfatase. The data inform the TS literature and indicate novel genetic mechanisms that may be of general significance to the neurobiology of attention.

Section snippets

Subjects

All experimental groups were generated on a random-bred MF1 albino strain background at the National Institute for Medical Research, United Kingdom, in pathogen-free isolators. Thirty-nine,XpO mice were generated from two subtly different crosses, based on a cross described previously (Evans and Phillips 1975): 40,In(X)1H/XPaf x 40,XY and 40,In(X)1HPaf/X x 40,XY, where In(X)1H represents a large chromosomal inversion and Paf is a small inversion that spans the pseudoautosomal boundary (Korobova

Comparison of 39,XpO and 39,XmO Mice Revealed No X-Linked Parent-of-Origin Effects on Behavior

As there were no significant differences between 39,XpO and 39,XmO mice on any behavioral measure (Supplementary Table 1), in all further analysis the two groups were pooled to form a single 39,XO group for comparison with 40,XX mice.

Equivalent Learning and Baseline Performance of the 5-CSRTT in 40,XX and 39,XO Mice

Initial learning of the task was equivalent in 40,XX and 39,XO mice indicating no effects on the basic ability to perform the task. Both groups of mice achieved high levels of accurate and rapid responding during training, taking an equivalent number of training

Discussion

We have shown, using a 39,XO mouse model, that the lack of an X chromosome is associated with specific deficits of discriminative response accuracy and reaction time in a continuous performance task, the 5-CSRTT. The behavioral differences most likely reflect effects on underlying attentional processes as they were emphasized under attentionally demanding task conditions and were alleviated using a task configuration with lower attentional demands (1-CSRTT). The X-monosomy effects, therefore,

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