Abstract
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.
基金项目
National Natural Science Foundation of China(31970920)
National Natural Science Foundation of China(31921002)
National Natural Science Foundation of China(31430037)
维普
万方数据