Tissue-specific variation of Ube3a protein expression in rodents and in a mouse model of Angelman syndrome.

Gustin RM, Bichell TJ, Bubser M, Daily J, Filonova I, Mrelashvili D, Deutch AY, Colbran RJ, Weeber EJ, Haas KF
Neurobiol Dis. 2010 39 (3): 283-91

PMID: 20423730 · PMCID: PMC2922926 · DOI:10.1016/j.nbd.2010.04.012

Angelman syndrome (AS) is a neurogenetic disorder caused by loss of maternal UBE3A expression or mutation-induced dysfunction of its protein product, the E3 ubiquitin-protein ligase, UBE3A. In humans and rodents, UBE3A/Ube3a transcript is maternally imprinted in several brain regions, but the distribution of native UBE3A/Ube3a(1) protein expression has not been comprehensively examined. To address this, we systematically evaluated Ube3a expression in the brain and peripheral tissues of wild-type (WT) and Ube3a maternal knockout mice (AS mice). Immunoblot and immunohistochemical analyses revealed a marked loss of 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 of AS mice showed greater than the predicted 50% reduction relative to WT mice. Co-localization studies showed Ube3a expression to be primarily neuronal in all brain regions and present in GABAergic interneurons as well as principal neurons. These findings suggest that neuronal function throughout the brain is compromised in AS.

MeSH Terms (15)

Analysis of Variance Angelman Syndrome Animals Blotting, Western Brain Disease Models, Animal gamma-Aminobutyric Acid Immunohistochemistry Liver Mice Mice, Knockout Myocardium Neurons Tissue Distribution Ubiquitin-Protein Ligases

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