Elsevier

Neuroscience Letters

Volume 487, Issue 2, 7 January 2011, Pages 129-133
Neuroscience Letters

Mitochondrial dysfunction in CA1 hippocampal neurons of the UBE3A deficient mouse model for Angelman syndrome

https://doi.org/10.1016/j.neulet.2009.06.079Get rights and content

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.

Section snippets

Acknowledgments

The authors thank Dr. Beaudet for providing the UBE3A deficient mice and establishing UC Irvine as a Rare Diseases Clinical Research site for the Angelman, Rett, and Prader–Willi Syndromes Consortium studies. This research was supported by the Rare Diseases Clinical Research Consortia (USA), 5 U54 RR019478-05 and an RDCRN postdoctoral trainee award (H.S.), R01AR050236 (V.E.K.), California Regenerative Medicine Predoctoral Fellowship TI-00008 (W.F.), the National Institute of Health (USA) grants

References (27)

  • O. Eeg-Olofsson et al.

    Rett syndrome: a mitochondrial disease?

    J. Child Neurol.

    (1990)
  • M. Escobar-Henriques et al.

    Regulation of mitochondrial fusion by the F-box protein Mdm30 involves proteasome-independent turnover of Fzo1

    J. Cell Biol.

    (2006)
  • A.P. Feinberg

    Phenotypic plasticity and the epigenetics of human disease

    Nature

    (2007)
  • Cited by (0)

    1

    Current address: Box 3528 Med Center, Department of Pediatrics, Division of Medical, Genetics, Duke University, Durham, NC 27710, USA.

    View full text