title: Differential gene expression reveals mitochondrial dysfunction in an imprinting center deletion mouse model of Prader-Willi syndrome.
abstract: 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. We focused our attention on the genes associated with energy metabolism and found that there were 95 and 66 mitochondrial genes differentially expressed in PWS muscle and brain, respectively. Assessment of enzyme activities of mitochondrial oxidative phosphorylation complexes in the brain, heart, liver, and muscle were assessed. We found the enzyme activities of the cardiac mitochondrial complexes II+‫III were up-regulated in the PWS imprinting center deletion mice compared to the wild-type littermates. These studies suggest that differential gene expression, especially of the mitochondrial genes may contribute to the pathophysiology of PWS.
authors.affiliation: Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, California, USA.
authors.forename: Puya G
authors.initials: PG
authors.lastname: Yazdi
authors.forename: Hailing
authors.initials: H
authors.lastname: Su
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ghimbovschi
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fan
authors.forename: Pinar E
authors.initials: PE
authors.lastname: Coskun
authors.forename: Angèle
authors.initials: A
authors.lastname: Nalbandian
authors.forename: Susan
authors.initials: S
authors.lastname: Knoblach
authors.forename: James L
authors.initials: JL
authors.lastname: Resnick
authors.forename: Eric
authors.initials: E
authors.lastname: Hoffman
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wallace
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Kimonis
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics; D016678:Genome / Q000235:genetics; D018392:Genomic Imprinting / Q000235:genetics*; D051379:Mice; D008928:Mitochondria / Q000235:genetics* / Q000473:pathology* / Q000648:ultrastructure; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011218:Prader-Willi Syndrome / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D045222:Electron Transport Chain Complex Proteins; D012333:RNA, Messenger
keywords: PWS-IC mouse model; Prader-Willi syndrome; differential gene expression