Institute of Reproductive and Regenerative Biology, Centre of Reproductive Medicine and Andrology, University Clinics, Muenster, Germany.
Acta Paediatr. 2011 Jun;100(6):885-91. doi: 10.1111/j.1651-2227.2010.02112.x. Epub 2011 Jan 17.
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.
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.
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.
Altered expression of genes escaping X inactivation probably contributes directly to the XX(Y)* phenotype.
我们假设克氏综合征（KS）患者不仅经历 X 染色体失活，而且某些基因逃避失活。由于男性代谢不能适应“女性样”的基因剂量，因此它们的转录本将构成显著差异。我们评估了 41 例 XX（Y）*男性小鼠中选定的 X 连锁基因的表达，以确定这些基因是否逃避失活以及是否存在组织特异性差异。
通过 Xist 表达鉴定正确的 X 染色体失活。通过实时 PCR 检测成年 XX（Y）和 XY雄性和 XX 雌性小鼠肝、肾和脑组织中 X 连锁基因的相对表达。
分析了已知逃避 X 染色体失活的基因的表达。从肝、肾和脑组织中定量了 Pgk1（对照，X 染色体失活）和逃避 X 染色体失活的基因 Eif2s3x、Kdm5c、Ddx3x 和 Kdm6a 的相对 mRNA 水平。Pgk1 mRNA 表达无差异，证实了正确的 X 染色体失活。在肾和肝组织中，XX（Y）男性在所有四个候选基因中的表达模式与女性相似，与 XY男性不同。相比之下，在脑组织中，XX（Y）*男性的四个基因表达均高于男性和女性对照。
逃避 X 染色体失活的基因表达的改变可能直接导致 XX（Y）*表型。
