Differential Gene Expression and Mitochondrial Dysfunction in Imprinting center deletion (PWS- IC del) Mouse model of Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is a genetic disorder caused by deficiency of imprinted gene expression from the paternal chromosome 15q11-15q13 and clinically characterized by neonatal hypotonia, short stature, cognitive impairment, hypogonadism, hyperphagia, morbid obesity and diabetes. Previous clinical studies suggest that a defect in energy metabolism may be involved in the pathogenesis of PWS. Assessment of enzyme activities of mitochondrial oxidative phosphorylation (OXPHOS) complexes in the brain, heart, liver and muscle were assessed. We used microarrays to detail the global programme of gene expression underlyingthe PWS and identified distinct classes of disregulated genes during this process. Skeletal (quadriceps) muscle Vastus Lateralis and whole brain samples from the mutant mice and their wild-type age-matched littermates were analyzed by microarray technology using the Mouse Genome 430 2.0 arrays (Affymetrix).

普拉德-威利综合征（Prader-Willi syndrome, PWS）是一种因父源15号染色体15q11-15q13区域印记基因表达缺失引发的遗传性疾病，临床特征表现为新生儿肌张力低下、身材矮小、认知障碍、性腺功能减退、食欲亢进、病态肥胖及糖尿病。既往临床研究提示，能量代谢缺陷可能参与普拉德-威利综合征的发病机制。本研究对脑组织、心脏、肝脏及肌肉组织中的线粒体氧化磷酸化（OXPHOS）复合物酶活性进行了检测。我们利用基因芯片（microarrays）技术解析了介导普拉德-威利综合征的全局基因表达程序，并在此过程中鉴定出多类失调基因。本研究采用小鼠基因组430 2.0芯片（Affymetrix公司），对突变小鼠及其年龄匹配的野生型同窝仔鼠的股外侧肌（股四头肌）骨骼肌样本与全脑组织样本进行了基因芯片分析。