| Mutation inε-Sarcoglycan Induces a Myoclonus-Dystonia Syndrome-Like Movement Disorder in Mice |
| |
| 引用本文： | Jiao Li,Yiqiong Liu,Qin Li,Xiaolin Huang,Dingxi Zhou,Hanjian Xu,Feng Zhao,Xiaoxiao Mi,Ruoxu Wang,Fan Jia,Fuqiang Xu,Jing Yang,Dong Liu,Xuliang Deng,Yan Zhang. Mutation inε-Sarcoglycan Induces a Myoclonus-Dystonia Syndrome-Like Movement Disorder in Mice[J]. 神经科学通报, 2021, 37(3): 311-322. DOI: 10.1007/s12264-020-00612-5 |
| |
| 作者姓名： | Jiao Li Yiqiong Liu Qin Li Xiaolin Huang Dingxi Zhou Hanjian Xu Feng Zhao Xiaoxiao Mi Ruoxu Wang Fan Jia Fuqiang Xu Jing Yang Dong Liu Xuliang Deng Yan Zhang |
| |
| 作者单位： | State Key Laboratory of Membrane Biology;Wuhan Institute of Physics and Mathematics;College of Life Sciences |
| |
| 基金项目： | supported by National Natural Science Foundation of China(31630028,91632305,and 91632303);the Fund for Distinguished Young Scholars of National Natural Science Foundation of China(81425009 and 81425007);the National Basic Science Research Program of China(2012CB933900 and 2015CB755600);the Strategic Priority Research Program(B)of China(XDB02050500)。 |
| |
| 摘 要： | Myoclonus dystonia syndrome(MDS)is an inherited movement disorder,and most MDS-related mutations have so far been found in theε-sarcoglycan(SGCE)coding gene.By generating SGCE-knockout(KO)and human 237 C>T mutation knock-in(KI)mice,we showed here that both KO and KI mice exerted typical movement defects similar to those of MDS patients.SGCE promoted filopodia development in vitro and inhibited excitatory synapse formation both in vivo and in vitro.Loss of function of SGCE leading to excessive excitatory synapses that may ultimately contribute to MDS pathology.Indeed,using a zebrafish MDS model,we found that among 1700 screened chemical compounds,Vigabatrin was the most potent in readily reversing MDS symptoms of mouse disease models.Our study strengthens the notion that mutations of SGCE lead to MDS and most likely,SGCE functions to brake synaptogenesis in the CNS.
|
| 关 键 词： | SGCE MDS FILOPODIA SYNAPSE EXCITABILITY |
| 收稿时间： | 2020-02-24 |
Mutation in ε-Sarcoglycan Induces a Myoclonus-Dystonia Syndrome-Like Movement Disorder in Mice |
| |
| Jiao Li,Yiqiong Liu,Qin Li,Xiaolin Huang,Dingxi Zhou,Hanjian Xu,Feng Zhao,Xiaoxiao Mi,Ruoxu Wang,Fan Jia,Fuqiang Xu,Jing Yang,Dong Liu,Xuliang Deng,Yan Zhang. Mutation in ε-Sarcoglycan Induces a Myoclonus-Dystonia Syndrome-Like Movement Disorder in Mice[J]. Neuroscience Bulletin, 2021, 37(3): 311-322. DOI: 10.1007/s12264-020-00612-5 |
| |
| Authors: | Jiao Li Yiqiong Liu Qin Li Xiaolin Huang Dingxi Zhou Hanjian Xu Feng Zhao Xiaoxiao Mi Ruoxu Wang Fan Jia Fuqiang Xu Jing Yang Dong Liu Xuliang Deng Yan Zhang |
| |
| Affiliation: | 1.State Key Laboratory of Membrane Biology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Peking University, Beijing, 100871 China ;2.Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071 China ;3.College of Life Sciences, Wuhan University, Wuhan, 430027 China |
| |
| Abstract: | Myoclonus dystonia syndrome (MDS) is an inherited movement disorder, and most MDS-related mutations have so far been found in the ε-sarcoglycan (SGCE) coding gene. By generating SGCE-knockout (KO) and human 237 C > T mutation knock-in (KI) mice, we showed here that both KO and KI mice exerted typical movement defects similar to those of MDS patients. SGCE promoted filopodia development in vitro and inhibited excitatory synapse formation both in vivo and in vitro. Loss of function of SGCE leading to excessive excitatory synapses that may ultimately contribute to MDS pathology. Indeed, using a zebrafish MDS model, we found that among 1700 screened chemical compounds, Vigabatrin was the most potent in readily reversing MDS symptoms of mouse disease models. Our study strengthens the notion that mutations of SGCE lead to MDS and most likely, SGCE functions to brake synaptogenesis in the CNS.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00612-5) contains supplementary material, which is available to authorized users. |
| |
| Keywords: | SGCE MDS Filopodia Synapse Excitability |
| 本文献已被 维普 等数据库收录！ |
|
