Induction of Anti-agrin Antibodies Causes Myasthenia Gravis in Mice

Min Yan, Ziyang Liu, Erkang Fei, Wenbing Chen, Xinsheng Lai, Bin Luo, Peng Chen, Hongyang Jing, Jin xiu Pan, Michael H. Rivner, Wen Cheng Xiong, Lin Mei

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction (NMJ). Most cases of MG are caused by autoantibodies against the acetylcholine receptor (AChR), muscle-specific kinase (MuSK) and low-density lipoprotein receptor-related protein 4 (LRP4). Recent studies have identified anti-agrin antibodies in MG patients lacking these three antibodies (i.e., triple negative MG). Agrin is a basal lamina protein that has two isoforms. Neural agrin (N-agrin) binds to LRP4 to activate MuSK to induce AChR clusters and is thus critical for NMJ formation. We demonstrate that mice immunized with N-agrin showed MG-associated symptoms including muscle weakness, fragmented and distorted NMJs. These effects were not observed in mice injected with muscle agrin (M-agrin), an isoform that is inactive in inducing AChR clusters. Treatment with anti-N-agrin, but not anti-M-agrin, antibodies reduced agrin-induced AChR clusters in muscle cells. Together, these observations suggest that agrin antibodies may be play a role in MG pathogenesis.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalNeuroscience
Volume373
DOIs
StatePublished - Mar 1 2018

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Keywords

  • agrin
  • antibodies
  • myasthenia gravis
  • neuromuscular junction

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Yan, M., Liu, Z., Fei, E., Chen, W., Lai, X., Luo, B., Chen, P., Jing, H., Pan, J. X., Rivner, M. H., Xiong, W. C., & Mei, L. (2018). Induction of Anti-agrin Antibodies Causes Myasthenia Gravis in Mice. Neuroscience, 373, 113-121. https://doi.org/10.1016/j.neuroscience.2018.01.015