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

Sci Rep 2017 08 16;7(1):8451. Epub 2017 Aug 16.

Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital and Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.

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.

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http://dx.doi.org/10.1038/s41598-017-08825-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559514PMC
August 2017
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