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, XX(Y)* 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 XX(Y)* 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, XX(Y)* males resembled the female expression pattern in all four candidate genes and were distinguishable from XY* males. Contrastingly, in brain tissue XX(Y)* males expressed all four genes higher than male and female controls. CONCLUSION: Altered expression of genes escaping X inactivation probably contributes directly to the XX(Y)* phenotype.
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, XX(Y)* 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 XX(Y)* 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, XX(Y)* males resembled the female expression pattern in all four candidate genes and were distinguishable from XY* males. Contrastingly, in brain tissue XX(Y)* males expressed all four genes higher than male and female controls. CONCLUSION: Altered expression of genes escaping X inactivation probably contributes directly to the XX(Y)* phenotype.
Authors: Arthur P Arnold; Karen Reue; Mansoureh Eghbali; Eric Vilain; Xuqi Chen; Negar Ghahramani; Yuichiro Itoh; Jingyuan Li; Jenny C Link; Tuck Ngun; Shayna M Williams-Burris Journal: Philos Trans R Soc Lond B Biol Sci Date: 2016-02-01 Impact factor: 6.237
Authors: Xuqi Chen; Shayna M Williams-Burris; Rebecca McClusky; Tuck C Ngun; Negar Ghahramani; Hayk Barseghyan; Karen Reue; Eric Vilain; Arthur P Arnold Journal: Biol Sex Differ Date: 2013-08-08 Impact factor: 5.027