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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559514/ https://www.ncbi.nlm.nih.gov/pubmed/28814801 http://dx.doi.org/10.1038/s41598-017-08825-x |
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author | Born, Heather A. Dao, An T. Levine, Amber T. Lee, Wai Ling Mehta, Natasha M. Mehra, Shubhangi Weeber, Edwin J. Anderson, Anne E. |
author_facet | Born, Heather A. Dao, An T. Levine, Amber T. Lee, Wai Ling Mehta, Natasha M. Mehra, Shubhangi Weeber, Edwin J. Anderson, Anne E. |
author_sort | Born, Heather A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5559514 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55595142017-08-18 Strain-dependence of the Angelman Syndrome phenotypes in Ube3a maternal deficiency mice Born, Heather A. Dao, An T. Levine, Amber T. Lee, Wai Ling Mehta, Natasha M. Mehra, Shubhangi Weeber, Edwin J. Anderson, Anne E. Sci Rep Article 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. Nature Publishing Group UK 2017-08-16 /pmc/articles/PMC5559514/ /pubmed/28814801 http://dx.doi.org/10.1038/s41598-017-08825-x Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Born, Heather A. Dao, An T. Levine, Amber T. Lee, Wai Ling Mehta, Natasha M. Mehra, Shubhangi Weeber, Edwin J. Anderson, Anne E. Strain-dependence of the Angelman Syndrome phenotypes in Ube3a maternal deficiency mice |
title | Strain-dependence of the Angelman Syndrome phenotypes in Ube3a maternal deficiency mice |
title_full | Strain-dependence of the Angelman Syndrome phenotypes in Ube3a maternal deficiency mice |
title_fullStr | Strain-dependence of the Angelman Syndrome phenotypes in Ube3a maternal deficiency mice |
title_full_unstemmed | Strain-dependence of the Angelman Syndrome phenotypes in Ube3a maternal deficiency mice |
title_short | Strain-dependence of the Angelman Syndrome phenotypes in Ube3a maternal deficiency mice |
title_sort | strain-dependence of the angelman syndrome phenotypes in ube3a maternal deficiency mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559514/ https://www.ncbi.nlm.nih.gov/pubmed/28814801 http://dx.doi.org/10.1038/s41598-017-08825-x |
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