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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...

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Autores principales: Xu, Dan, Zhi, Yiqiang, Liu, Xinyi, Guan, Le, Yu, Jurui, Zhang, Dan, Zhang, Weiya, Wang, Yaqing, Tao, Wucheng, Xu, Zhiheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Nature Singapore 2022
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.
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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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