Voor het Angelman Syndroom

pdf Tissue-specific variation of Ube3a protein expression in rodents and in a mousemodel of AS Populair

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Gustin RM 2010 Neurobiol Dis 39-283.pdf

Angelman syndrome (AS) is a neurogenetic disorder caused by loss of maternal UBE3A expression ormutation-induced dysfunction of its protein product, the E3 ubiquitin?protein ligase, UBE3A. In humans androdents, UBE3A/Ube3a transcript is maternally imprinted in several brain regions, but the distribution ofnative UBE3A/Ube3a1 protein expression has not been comprehensively examined. To address this, wesystematically evaluated Ube3a expression in the brain and peripheral tissues of wild-type (WT) and Ube3amaternal knockout mice (AS mice). Immunoblot and immunohistochemical analyses revealed a marked lossof Ube3a protein in hippocampus, hypothalamus, olfactory bulb, cerebral cortex, striatum, thalamus,midbrain, and cerebellum in AS mice relative to WT littermates. Also, Ube3a expression in heart and liver ofAS mice showed greater than the predicted 50% reduction relative to WT mice. Co-localization studiesshowed Ube3a expression to be primarily neuronal in all brain regions and present in GABAergicinterneurons as well as principal neurons. These findings suggest that neuronal function throughout thebrain is compromised in AS.

Richard Gustin, Terry Jo Bichell, Michael Bubser, Jennifer Daily, Irina Filonova, Davit Mrelashvili, Ariel Y. Deutch, Roger J. Colbran, Edwin J. Weeber, Kevin F. Haas

Neurobiology of Disease 39 (2010) 283?291