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

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 con...

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Autores principales:	Heather A. Born, An T. Dao, Amber T. Levine, Wai Ling Lee, Natasha M. Mehta, Shubhangi Mehra, Edwin J. Weeber, Anne E. Anderson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f0286cef58f8494082fc0f0267c3148a
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spelling	oai:doaj.org-article:f0286cef58f8494082fc0f0267c3148a2021-12-02T16:08:09ZStrain-dependence of the Angelman Syndrome phenotypes in Ube3a maternal deficiency mice10.1038/s41598-017-08825-x2045-2322https://doaj.org/article/f0286cef58f8494082fc0f0267c3148a2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08825-xhttps://doaj.org/toc/2045-2322Abstract 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.Heather A. BornAn T. DaoAmber T. LevineWai Ling LeeNatasha M. MehtaShubhangi MehraEdwin J. WeeberAnne E. AndersonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Heather A. Born An T. Dao Amber T. Levine Wai Ling Lee Natasha M. Mehta Shubhangi Mehra Edwin J. Weeber Anne E. Anderson Strain-dependence of the Angelman Syndrome phenotypes in Ube3a maternal deficiency mice
description	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/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	article
author	Heather A. Born An T. Dao Amber T. Levine Wai Ling Lee Natasha M. Mehta Shubhangi Mehra Edwin J. Weeber Anne E. Anderson
author_facet	Heather A. Born An T. Dao Amber T. Levine Wai Ling Lee Natasha M. Mehta Shubhangi Mehra Edwin J. Weeber Anne E. Anderson
author_sort	Heather A. Born
title	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_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_sort	strain-dependence of the angelman syndrome phenotypes in ube3a maternal deficiency mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f0286cef58f8494082fc0f0267c3148a
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Strain-dependence of the Angelman Syndrome phenotypes in Ube3a maternal deficiency mice

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