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WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice
Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Nature Singapore
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10465473/ https://www.ncbi.nlm.nih.gov/pubmed/36571716 http://dx.doi.org/10.1007/s12264-022-00997-5 |
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author | Xu, Dan Zhi, Yiqiang Liu, Xinyi Guan, Le Yu, Jurui Zhang, Dan Zhang, Weiya Wang, Yaqing Tao, Wucheng Xu, Zhiheng |
author_facet | Xu, Dan Zhi, Yiqiang Liu, Xinyi Guan, Le Yu, Jurui Zhang, Dan Zhang, Weiya Wang, Yaqing Tao, Wucheng Xu, Zhiheng |
author_sort | Xu, Dan |
collection | PubMed |
description | Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-022-00997-5. |
format | Online Article Text |
id | pubmed-10465473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Nature Singapore |
record_format | MEDLINE/PubMed |
spelling | pubmed-104654732023-08-31 WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice Xu, Dan Zhi, Yiqiang Liu, Xinyi Guan, Le Yu, Jurui Zhang, Dan Zhang, Weiya Wang, Yaqing Tao, Wucheng Xu, Zhiheng Neurosci Bull Original Article Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-022-00997-5. Springer Nature Singapore 2022-12-26 /pmc/articles/PMC10465473/ /pubmed/36571716 http://dx.doi.org/10.1007/s12264-022-00997-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Xu, Dan Zhi, Yiqiang Liu, Xinyi Guan, Le Yu, Jurui Zhang, Dan Zhang, Weiya Wang, Yaqing Tao, Wucheng Xu, Zhiheng WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice |
title | WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice |
title_full | WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice |
title_fullStr | WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice |
title_full_unstemmed | WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice |
title_short | WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice |
title_sort | wdr62-deficiency causes autism-like behaviors independent of microcephaly in mice |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10465473/ https://www.ncbi.nlm.nih.gov/pubmed/36571716 http://dx.doi.org/10.1007/s12264-022-00997-5 |
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