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.