title: Mitochondrial dysfunction in CA1 hippocampal neurons of the UBE3A deficient mouse model for Angelman syndrome.
abstract: Angelman syndrome (AS) is a severe neurological disorder caused by a deficiency of ubiquitin protein ligase E3A (UBE3A), but the pathophysiology of the disease remains unknown. We now report that in the brains of AS mice in which the maternal UBE3A allele is mutated (m-) and the paternal allele is potentially inactivated by imprinting (p+) (UBE3A m-\p+), the mitochondria are abnormal and exhibit a partial oxidative phosphorylation (OXPHOS) defect. Electron microscopy of the hippocampal region of the UBE3A m-\p+ mice (n=6) reveals small, dense mitochondria with altered cristae, relative to wild-type littermates (n=6) and reduced synaptic vesicle density. The specific activity of OXPHOS complex III is reduced in whole brain mitochondria in UBE3A m-\p+ (n=5) mice versus wild-type littermates (n=5). Therefore, mitochondrial dysfunction may contribute to the pathophysiology of Angelman syndrome.
authors: Department of Pediatrics, Division of Genetics and Metabolism, University of California, Irvine, CA 92697, USA.
authors: Hailing
authors: H
authors: Su
authors: Weiwei
authors: W
authors: Fan
authors: Pinar E
authors: PE
authors: Coskun
authors: Jouni
authors: J
authors: Vesa
authors: June-Anne
authors: JA
authors: Gold
authors: Yong-Hui
authors: YH
authors: Jiang
authors: Prasanth
authors: P
authors: Potluri
authors: Vincent
authors: V
authors: Procaccio
authors: Allan
authors: A
authors: Acab
authors: John H
authors: JH
authors: Weiss
authors: Douglas C
authors: DC
authors: Wallace
authors: Virginia E
authors: VE
authors: Kimonis
mesh_terms: D017204:Angelman Syndrome / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009474:Neurons / Q000201:enzymology* / Q000473:pathology / Q000502:physiology; D011689:Purkinje Cells / Q000201:enzymology / Q000473:pathology; D013572:Synaptic Vesicles / Q000235:genetics / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics
chemical_list: C502429:Ube3a protein, mouse; D044767:Ubiquitin-Protein Ligases