Expression of selected genes escaping from X inactivation in the 41, XX(Y)* mouse model for Klinefelter's syndrome.
OBJECTIVE
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.


CONCLUSIONS
Altered expression of genes escaping X inactivation probably contributes directly to the XX(Y)* phenotype.
Institute of Reproductive and Regenerative Biology, Centre of Reproductive Medicine and Andrology, University Clinics, Muenster, Germany.
Steffi
S
Werler
Andreas
A
Poplinski
Jörg
J
Gromoll
Joachim
J
Wistuba
D000818:Animals; D001921:Brain / Q000378:metabolism; D053487:DEAD-box RNA Helicases; D004195:Disease Models, Animal; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007668:Kidney / Q000378:metabolism; D007713:Klinefelter Syndrome / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D010735:Phosphoglycerate Kinase / Q000235:genetics / Q000378:metabolism; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D049951:X Chromosome Inactivation / Q000235:genetics*
D015852:Eukaryotic Initiation Factor-2; D012333:RNA, Messenger; C528165:Pgk1 protein, mouse; D010735:Phosphoglycerate Kinase; D053487:DEAD-box RNA Helicases; C514697:Ddx3x protein, mouse; D020365:RNA Helicases