Expression of selected genes escaping from X inactivation in the 41, XXY* mouse model for Klinefelter’s syndrome
Article first published online: 17 JAN 2011
© 2011 The Author(s)/Acta Pædiatrica © 2011 Foundation Acta Pædiatrica
Volume 100, Issue 6, pages 885–891, June 2011
How to Cite
Werler, S., Poplinski, A., Gromoll, J. and Wistuba, J. (2011), Expression of selected genes escaping from X inactivation in the 41, XXY* mouse model for Klinefelter’s syndrome. Acta Paediatrica, 100: 885–891. doi: 10.1111/j.1651-2227.2010.02112.x
- Issue published online: 27 APR 2011
- Article first published online: 17 JAN 2011
- Received 1 September 2010; revised 23 November 2010; accepted 29 November 2010.
- Gene expression;
- Klinefelter’s syndrome;
- X inactivation;
- XXY* mouse
Aim: We hypothesized that patients with Klinefelter’s syndrome (KS) not only undergo X inactivation, but also that genes escape from inactivation. Their transcripts would constitute a significant difference, as male metabolism is not adapted to a ‘female-like’ gene dosage. We evaluated the expression of selected X-linked genes in our 41, XXY* male mice to determine whether these genes escape inactivation and whether tissue-specific differences occur.
Methods: Correct X inactivation was identified by Xist expression. Relative expression of X-linked genes was examined in liver, kidney and brain tissue by real-time PCR in adult XXY* and XY* males and XX females.
Results: Expression of genes known to escape X inactivation was analysed. Relative mRNA levels of Pgk1 (control, X inactivated), and the genes Eif2s3x, Kdm5c, Ddx3x and Kdm6a escaping from X inactivation were quantified from liver, kidney and brain. Pgk1 mRNA expression showed no difference, confirming correct X inactivation. In kidney and liver, XXY* males resembled the female expression pattern in all four candidate genes and were distinguishable from XY* males. Contrastingly, in brain tissue XXY* males expressed all four genes higher than male and female controls.
Conclusion: Altered expression of genes escaping X inactivation probably contributes directly to the XXY* phenotype.