1. Immunization of mice with LRP4 induces myasthenia similar to MuSK-associated myasthenia gravis
- Author
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Masahiko Kishi, Rumi Takashima, Kazuhiro Shigemoto, Norio Motohashi, Shuuichi Mori, and Hiroshi Nishimune
- Subjects
0301 basic medicine ,Active immunization ,Neuromuscular junction ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Developmental Neuroscience ,Antigen ,Myasthenia Gravis ,medicine ,Animals ,Humans ,LDL-Receptor Related Proteins ,Muscle Weakness ,biology ,business.industry ,Autoantibody ,Receptor Protein-Tyrosine Kinases ,Muscle weakness ,medicine.disease ,Virology ,Myasthenia gravis ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Immunization ,Immunology ,biology.protein ,Female ,Antibody ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Since the first report of experimental animal models of myasthenia gravis (MG) with autoantibodies against low-density lipoprotein receptor-related protein 4 (LRP4), there have not been any major reports replicating the pathogenicity of anti-LRP4 antibodies (Abs). Recent clinical studies have cast doubt on the specificity and pathogenicity of anti-LRP4 antibodies for MG, highlighting the need for further research. In this study, we purified antigens corresponding to the extracellular region of human LRP4 stably expressed with chaperones in 293 cells and used these antigens to immunize female A/J mice. Immunization with LRP4 protein caused mice to develop myasthenia having similar electrophysiological and histological features as are observed in MG patients with circulating Abs against muscle-specific kinase (MuSK). Our results clearly demonstrate that active immunization of mice with LRP4 proteins causes myasthenia similar to the MG induced by anti-MuSK Abs. Further experimental and clinical studies are required to prove the pathogenicity of anti-LRP4 Abs in MG patients.
- Published
- 2017