Induction of Anti-agrin Antibodies Causes Myasthenia Gravis in Mice.
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.
['Yan|Min|M|', 'Liu|Ziyang|Z|', 'Fei|Erkang|E|', 'Chen|Wenbing|W|', 'Lai|Xinsheng|X|', 'Luo|Bin|B|', 'Chen|Peng|P|', 'Jing|Hongyang|H|', 'Pan|Jin-Xiu|JX|', 'Rivner|Michael H|MH|', 'Xiong|Wen-Cheng|WC|', 'Mei|Lin|L|']
D018171:Agrin D000818:Animals D001323:Autoantibodies D004195:Disease Models, Animal D004926:Escherichia coli D005260:Female D007114:Immunization D051379:Mice D053580:Muscle Strength D018482:Muscle, Skeletal D009157:Myasthenia Gravis D009469:Neuromuscular Junction D020033:Protein Isoforms D011950:Receptors, Cholinergic D011994:Recombinant Proteins
antibodies myasthenia gravis neuromuscular junction agrin