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

Hailing Su; Weiwei Fan; Pinar E. Coskun; Jouni Vesa; June Anne Gold; Yong Hui Jiang; Prasanth Potluri; Vincent Procaccio; Allan Acab; John H. Weiss; Douglas C. Wallace; Virginia E. Kimonis

doi:10.1016/j.neulet.2009.06.079

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

Hailing Su
, Weiwei Fan
, Pinar E. Coskun
, Jouni Vesa
, June Anne Gold
, Yong Hui Jiang
, Prasanth Potluri
, Vincent Procaccio
, Allan Acab
, John H. Weiss
, Douglas C. Wallace
, Virginia E. Kimonis

Producción científica: Article › revisión exhaustiva

62 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	129-133
Número de páginas	5
Publicación	Neuroscience Letters
Volumen	487
N.º	2
DOI	https://doi.org/10.1016/j.neulet.2009.06.079
Estado	Published - ene 7 2011

Financiación

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 NS21328, NS41850, AG13154, AG24373 and AG16573 (D.C.W.).

Financiadores	Número del financiador
California Institute for Regenerative Medicine	TI-00008
Rare Diseases Clinical Research Consortia	R01AR050236, 5 U54 RR019478-05
National Institutes of Health (NIH)	AG24373, NS21328, NS41850, AG16573, AG13154
Eunice Kennedy Shriver National Institute of Child Health and Human Development	K12HD043494

ASJC Scopus subject areas

General Neuroscience

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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-\textbackslash{}p+), the mitochondria are abnormal and exhibit a partial oxidative phosphorylation (OXPHOS) defect. Electron microscopy of the hippocampal region of the UBE3A m-\textbackslash{}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-\textbackslash{}p+ (n= 5) mice versus wild-type littermates (n= 5). Therefore, mitochondrial dysfunction may contribute to the pathophysiology of Angelman syndrome.",

keywords = "Angelman syndrome, Electron microscopy, Mitochondrial complexes, Synaptic vesicle, UBE3A deficient mouse",

author = "Hailing Su and Weiwei Fan and Coskun, \{Pinar E.\} and Jouni Vesa and Gold, \{June Anne\} and Jiang, \{Yong Hui\} and Prasanth Potluri and Vincent Procaccio and Allan Acab and Weiss, \{John H.\} and Wallace, \{Douglas C.\} and Kimonis, \{Virginia E.\}",

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AU - Su, Hailing

AU - Fan, Weiwei

AU - Coskun, Pinar E.

AU - Vesa, Jouni

AU - Gold, June Anne

AU - Jiang, Yong Hui

AU - Potluri, Prasanth

AU - Procaccio, Vincent

AU - Acab, Allan

AU - Weiss, John H.

AU - Wallace, Douglas C.

AU - Kimonis, Virginia E.

PY - 2011/1/7

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N2 - 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.

AB - 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.

KW - Angelman syndrome

KW - Electron microscopy

KW - Mitochondrial complexes

KW - Synaptic vesicle

KW - UBE3A deficient mouse

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

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