ASH1L haploinsufficiency results in autistic-like phenotypes in mice and links Eph receptor gene to autism spectrum disorder

doi:10.1016/j.neuron.2021.12.035

	ASH1L haploinsufficiency results in autistic-like phenotypes in mice and links Eph receptor gene to autism spectrum disorder
	Yan, Yuze1,2 ; Tian, Miaomiao 1,2; Li, Meng1 ; Zhou, Gang1 ; Chen, Qinan1 ; Xu, Mingrui 6,7; Hu, Yi 1,2; Luo, Wenhan1 ; Guo, Xiuxian1 ; Zhang, Cheng 8,9; Xie, Hong 3,4; Wu, Qing-Feng 5,6,7; Xiong, Wei 2; Liu, Shiguo 8,9; Guan, Ji-Song1,5
	2022-04-06
发表期刊	NEURON (IF:14.7[JCR-2023],16.9[5-Year])
ISSN	0896-6273
EISSN	1097-4199
卷号	110 期号:7
发表状态	已发表
DOI	10.1016/j.neuron.2021.12.035
摘要	ASD-associated genes are enriched for synaptic proteins and epigenetic regulators. How those chromatin modulators establish ASD traits have remained unknown. We find haploinsufficiency of Ash1l causally induces anxiety and autistic-like behavior, including repetitive behavior, and alters social behavior. Specific depletion of Ash1l in forebrain induces similar ASD-associated behavioral defects. While the learning ability remains intact, the discrimination ability of Ash1l mutant mice is reduced. Mechanistically, deletion of AshIl in neurons induces excessive synapses due to the synapse pruning deficits, especially during the post-learning period. Dysregulation of synaptic genes is detected in Ash1l mutant brain. Specifically, Eph receptor A7 is downregulated in Ash1l(+/-) mice through accumulating EZH2-mediated H3K27me3 in its gene body. Importantly, increasing activation of EphA7 in Ash1l(+/-) mice by supplying its ligand, ephrin-A5, strongly promotes synapse pruning and rescues discrimination deficits. Our results suggest that Ash1l haploinsufficiency is a highly penetrant risk factor for ASD, resulting from synapse pruning deficits.
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收录类别	SCI ; SCIE
语种	英语
资助项目	Science & Technology Innovation 2030 Project of China[2021ZD0203500] ; NSFC[31970903,31671104,31371059] ; Shanghai Ministry of Science and Technology[19ZR1477400] ; National Natural Science Foundation of China[61621136008] ; German Research Foundation (DFG)[TRR-169] ; STCSM[18JC1420301]
WOS研究方向	Neurosciences & Neurology
WOS类目	Neurosciences
WOS记录号	WOS:000786147500010
出版者	CELL PRESS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/180906
专题	生命科学与技术学院_PI研究组_管吉松组生命科学与技术学院_硕士生生命科学与技术学院_博士生
通讯作者	Xiong, Wei; Liu, Shiguo; Guan, Ji-Song
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China 3.Univ Shanghai Sci & Technol, Inst Photon Chips, Shanghai 200093, Peoples R China 4.Univ Shanghai Sci & Technol, Sch Hlth Sci & Engn, Shanghai 200093, Peoples R China 5.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai 200031, Peoples R China 6.Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing 100101, Peoples R China 7.Univ Chinese Acad Sci, Beijing 100101, Peoples R China 8.Qingdao Univ, Med Genet Dept, Affiliated Hosp, Qingdao 266071, Peoples R China 9.Qingdao Univ, Prenatal Diag Ctr, Affiliated Hosp, Qingdao 266071, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Yan, Yuze,Tian, Miaomiao,Li, Meng,et al. ASH1L haploinsufficiency results in autistic-like phenotypes in mice and links Eph receptor gene to autism spectrum disorder[J]. NEURON,2022,110(7).
APA	Yan, Yuze.,Tian, Miaomiao.,Li, Meng.,Zhou, Gang.,Chen, Qinan.,...&Guan, Ji-Song.(2022).ASH1L haploinsufficiency results in autistic-like phenotypes in mice and links Eph receptor gene to autism spectrum disorder.NEURON,110(7).
MLA	Yan, Yuze,et al."ASH1L haploinsufficiency results in autistic-like phenotypes in mice and links Eph receptor gene to autism spectrum disorder".NEURON 110.7(2022).