| First Author | Yan M | Year | 2018 |
| Journal | Neuroscience | Volume | 373 |
| Pages | 113-121 | PubMed ID | 29339325 |
| Mgi Jnum | J:258113 | Mgi Id | MGI:6121234 |
| Doi | 10.1016/j.neuroscience.2018.01.015 | Citation | Yan M, et al. (2018) Induction of Anti-agrin Antibodies Causes Myasthenia Gravis in Mice. Neuroscience 373:113-121 |
| abstractText | 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. |
