Mutation in ε-Sarcoglycan Induces a Myoclonus-Dystonia Syndrome-Like Movement Disorder in Mice

• 作者: 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
• 来源期刊: 神经科学通报（英文版）
• 年，卷（期）: 2021,（3）
• 所属期刊栏目: Original Articles
• 页码范围: 311-322
• 页数: 12页
• 语种: 英文

摘要

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.