Strain-dependence of the Angelman Syndrome phenotypes in Ube3a maternal deficiency mice

Angelman syndrome (AS) is a genetic neurodevelopmental disorder, most commonly caused by deletion or mutation of the maternal allele of the UBE3A gene, with behavioral phenotypes and seizures as key features. Currently no treatment is available, and therapeutics are often ineffective in controlling...

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Bibliographic Details
Published in:Scientific reports 2017-08, Vol.7 (1), p.8451-15, Article 8451
Main Authors: Born, Heather A., Dao, An T., Levine, Amber T., Lee, Wai Ling, Mehta, Natasha M., Mehra, Shubhangi, Weeber, Edwin J., Anderson, Anne E.
Format: Article
Language:English
Subjects:
631/378/1689/178
631/378/1689/2608
631/378/3920
64/60
Anxiety
Behavior
Convulsions & seizures
Cortex
EEG
Fear conditioning
Gene deletion
Genotype & phenotype
Hippocampus
Humanities and Social Sciences
multidisciplinary
Mutation
Neurodevelopmental disorders
Proteins
Science
Science (multidisciplinary)
Seizures
Ubiquitin-protein ligase
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Summary:Angelman syndrome (AS) is a genetic neurodevelopmental disorder, most commonly caused by deletion or mutation of the maternal allele of the UBE3A gene, with behavioral phenotypes and seizures as key features. Currently no treatment is available, and therapeutics are often ineffective in controlling AS-associated seizures. Previous publications using the Ube3a maternal deletion model have shown behavioral and seizure susceptibility phenotypes, however findings have been variable and merit characterization of electroencephalographic (EEG) activity. In this study, we extend previous studies comparing the effect of genetic background on the AS phenotype by investigating the behavioral profile, EEG activity, and seizure threshold. AS C57BL/6J mice displayed robust behavioral impairments, spontaneous EEG polyspikes, and increased cortical and hippocampal power primarily driven by delta and theta frequencies. AS 129 mice performed poorly on wire hang and contextual fear conditioning and exhibited a lower seizure threshold and altered spectral power. AS F1 hybrid mice (C57BL/6J × 129) showed milder behavioral impairments, infrequent EEG polyspikes, and fewer spectral power alterations. These findings indicate the effect of common genetic backgrounds on the Ube3a maternal deletion behavioral, EEG, and seizure threshold phenotypes. Our results will inform future studies on the optimal strain for evaluating therapeutics with different AS-like phenotypes.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-08825-x