Base-edited cynomolgus monkeys mimic core symptoms of STXBP1 encephalopathy

doi:10.1016/j.ymthe.2022.03.001

	Base-edited cynomolgus monkeys mimic core symptoms of STXBP1 encephalopathy
	Lu, Zongyang1,2,6 ; He, Siting 1,3; Jiang, Jian 1,4; Zhuang, Ling 1,3; Wang, Yan 1; Yang, Guang2 ; Jiang, Xiaoyu 1; Nie, Yanhong 1; Fu, Jiqiang 1; Zhang, Xiaotong 1; Lu, Yong 1; Bian, Xinyan 1; Chang, Hung-Chun 1,4; Xiong, Zhiqi 1; Huang, Xingxu2,5 ; Liu, Zhen 1,6; Sun, Qiang 1,6
	2022-06-01
发表期刊	MOLECULAR THERAPY (IF:12.1[JCR-2023],11.8[5-Year])
ISSN	1525-0016
EISSN	1525-0024
卷号	30 期号:6
发表状态	已发表
DOI	10.1016/j.ymthe.2022.03.001
摘要	Presynaptic syntaxin binding protein 1 (STXBP1) is essential for neurotransmitter release. Heterozygous mutations in this protein cause STXBP1 encephalopathy (STXBP1-E), which is characterized by intellectual disabilities and epilepsies. Since nonhuman primates closely resemble humans, monkey models may advance studies on the pathogenesis and therapeutic treatments of STXBP1-E. We generated cynomolgus monkeys carrying STXBP1 (R292H) mutation through base editing of in vitro fertilized embryos to mimic a clinical condition. The newborn STXBP1-edited monkeys exhibited focal epilepsy, and the animal that survived beyond the first week postpartum presented typical EEG phenotypes. Biochemical analysis of brain biopsy samples showed reduced levels of STXBP1 (MUNC18-1) and SNARE complex proteins. Single-cell sequencing identified one specific cell cluster that may contribute to encephalopathy. Thus, our case report shows that base-edited STXBP1 mutant monkeys are a good animal model for STXBP1-E, and that a base-editing approach is useful for generating primate models of human genetic disorders.
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收录类别	SCI ; SCIE
语种	英语
资助项目	Shanghai Municipal Science and Technology Major Project[2018SHZDZX05] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB32060000] ; National Natural Science Foundation of China["31825018","82021001","81671516"] ; Basic Frontier Scientific Research Program of Chinese Academy of Sciences From 0 to 1 original innovation project[ZDBS-LY-SM019] ; China National Postdoctoral Program for Innovative Talents[BX20200350]
WOS研究方向	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
WOS类目	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
WOS记录号	WOS:000829670100010
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/214764
专题	生命科学与技术学院_博士生生命科学与技术学院_PI研究组_黄行许组
通讯作者	Huang, Xingxu; Liu, Zhen; Sun, Qiang
作者单位	1.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, CAS Key Lab Primate Neurobiol, State Key Lab Neurosci,Inst Neurosci, Shanghai, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Inst Neurosci, Dynam Brain Signal Anal Facil, Shanghai 200031, Peoples R China 5.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China 6.Shanghai Ctr Brain Sci & Brain Inspired Intellige, Shanghai 201210, 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
推荐引用方式 GB/T 7714	Lu, Zongyang,He, Siting,Jiang, Jian,et al. Base-edited cynomolgus monkeys mimic core symptoms of STXBP1 encephalopathy[J]. MOLECULAR THERAPY,2022,30(6).
APA	Lu, Zongyang.,He, Siting.,Jiang, Jian.,Zhuang, Ling.,Wang, Yan.,...&Sun, Qiang.(2022).Base-edited cynomolgus monkeys mimic core symptoms of STXBP1 encephalopathy.MOLECULAR THERAPY,30(6).
MLA	Lu, Zongyang,et al."Base-edited cynomolgus monkeys mimic core symptoms of STXBP1 encephalopathy".MOLECULAR THERAPY 30.6(2022).