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Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors
Autism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causality and underlying m...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213741/ https://www.ncbi.nlm.nih.gov/pubmed/34145365 http://dx.doi.org/10.1038/s42003-021-02282-z |
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author | Gao, Yuen Duque-Wilckens, Natalia Aljazi, Mohammad B. Wu, Yan Moeser, Adam J. Mias, George I. Robison, Alfred J. He, Jin |
author_facet | Gao, Yuen Duque-Wilckens, Natalia Aljazi, Mohammad B. Wu, Yan Moeser, Adam J. Mias, George I. Robison, Alfred J. He, Jin |
author_sort | Gao, Yuen |
collection | PubMed |
description | Autism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causality and underlying molecular mechanisms linking ASH1L mutations to genesis of ASD/ID remain undetermined. Here we show loss of ASH1L in the developing mouse brain is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes an ASD/ID mouse model revealing the critical function of an epigenetic factor ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities. |
format | Online Article Text |
id | pubmed-8213741 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-82137412021-07-01 Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors Gao, Yuen Duque-Wilckens, Natalia Aljazi, Mohammad B. Wu, Yan Moeser, Adam J. Mias, George I. Robison, Alfred J. He, Jin Commun Biol Article Autism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causality and underlying molecular mechanisms linking ASH1L mutations to genesis of ASD/ID remain undetermined. Here we show loss of ASH1L in the developing mouse brain is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes an ASD/ID mouse model revealing the critical function of an epigenetic factor ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities. Nature Publishing Group UK 2021-06-18 /pmc/articles/PMC8213741/ /pubmed/34145365 http://dx.doi.org/10.1038/s42003-021-02282-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Gao, Yuen Duque-Wilckens, Natalia Aljazi, Mohammad B. Wu, Yan Moeser, Adam J. Mias, George I. Robison, Alfred J. He, Jin Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors |
title | Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors |
title_full | Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors |
title_fullStr | Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors |
title_full_unstemmed | Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors |
title_short | Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors |
title_sort | loss of histone methyltransferase ash1l in the developing mouse brain causes autistic-like behaviors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213741/ https://www.ncbi.nlm.nih.gov/pubmed/34145365 http://dx.doi.org/10.1038/s42003-021-02282-z |
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