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Strain-dependence of the Angelman Syndrome phenotypes in Ube3a maternal deficiency mice.
- Source :
-
Scientific reports [Sci Rep] 2017 Aug 16; Vol. 7 (1), pp. 8451. Date of Electronic Publication: 2017 Aug 16. - Publication Year :
- 2017
-
Abstract
- 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/6Jā×ā129) 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.
- Subjects :
- Angelman Syndrome genetics
Angelman Syndrome physiopathology
Animals
Electroencephalography
Fear physiology
Female
Male
Maze Learning physiology
Memory physiology
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Knockout
Motor Activity physiology
Phenotype
Seizures genetics
Seizures physiopathology
Species Specificity
Ubiquitin-Protein Ligases genetics
Angelman Syndrome metabolism
Disease Models, Animal
Seizures metabolism
Ubiquitin-Protein Ligases deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28814801
- Full Text :
- https://doi.org/10.1038/s41598-017-08825-x