首页|WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice

WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice

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Brain size abnormality is correlated with an increased frequency of autism spectrum disorder(ASD)in offspring.Genetic analysis indicates that heterozygous muta-tions 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 interac-tions and repetitive behaviors.WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cor-tical pyramidal neurons.Finally,we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency,probably by comple-menting 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.

WDR62MicrocephalyAutism spectrum disorderSynapseRetinoic acid

Dan Xu、Yiqiang Zhi、Xinyi Liu、Le Guan、Jurui Yu、Dan Zhang、Weiya Zhang、Yaqing Wang、Wucheng Tao、Zhiheng Xu

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Fujian Key Laboratory of Molecular Neurology,Institute of Neuroscience,Fujian Medical University,Fuzhou 350005,China

College of Biological Science and Engineering,Institute of Life Sciences,Fuzhou University,Fuzhou 350108,China

University of Chinese Academy of Sciences,Beijing 100101,China

State Key Laboratory of Molecular Developmental Biology,CAS Center for Excellence in Brain Science and Intelligence Technology,Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing 100101,China

Key Laboratory of Brain Aging and Neurodegenerative Diseases,School of Basic Medical Sciences,Fujian Medical University,Fuzhou 350108,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of China

319709203192100231430037

2023

10.1007/s12264-022-00997-5

神经科学通报(英文版)
中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD
影响因子：0.741
ISSN：1673-7067
年,卷(期)：2023.39(9)
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