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

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.

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Acknowledgements

This work was 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).

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Correspondence to Xuliang Deng or Yan Zhang.

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Li, J., Liu, Y., Li, Q. et al. Mutation in ε-Sarcoglycan Induces a Myoclonus-Dystonia Syndrome-Like Movement Disorder in Mice. Neurosci. Bull. (2020). https://doi.org/10.1007/s12264-020-00612-5

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Keywords

  • SGCE
  • MDS
  • Filopodia
  • Synapse
  • Excitability