Utility of experimental animal models of myasthenia gravis for the elucidation of pathogenic mechanisms and development of new medications

Abstract

Myasthenia gravis (MG) is an autoimmune disease characterized by ptosis, fatigue and muscle weakness, caused by the association of pathogenic autoantibodies with postsynaptic membrane proteins at neuromuscular junctions. Although various autoantibodies have been found in sera from patients with MG, causal relationships with MG have not been shown for most antibodies. Establishment of the pathogenicity of candidate antibodies with experimental animal models of myasthenia gravis is indispensable. The pathogenicity of autoantibodies against acetylcholine receptors and musclespecific kinase has been confirmed by active immunization with purified antigens or by passive transfer of autoantibodies from patients with MG. Furthermore, animal models of MG have shown not only the pathogenic mechanisms underlying the manifestation of muscle weakness and atrophy observed in patients with MG, but also the efficacy of novel therapies and the adverse effects of therapeutic drugs. Here, we review the contributions of animal MG models to the elucidation of the pathogenic mechanisms of MG and the development of medications for the disease.

Approach to the unraveled questions over neuromuscular junction diseases

“…Mori and Shigemoto wrote an excellent review about animal models of MG. 4 Animal models are essential to elucidating the mechanisms of diseases. That is also the case in neuromuscular diseases, such as MG, especially because they are useful to show the roles of autoantibodies found in patients' sera.…”