Induction of a mouse model of myasthenia gravis by acetylcholine receptor site-specific autoantibody production.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07766
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Toho University
• Principal Investigator: KONNO SHINGO 東邦大学, 医学部, 准教授 (50459765)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 重症筋無力症 / AChR α subunit

Outline of Final Research Achievements

B57BL6／J mice were immunized with a peptide corresponding to the major immunogenic region of the acetylcholine receptor α1 subunit and an adjuvant. Antibodies to the peptide used for immunization and to the recombinant protein of the acetylcholine receptor α1 subunit were detected in the serum of the mice after 8 weeks of immunization. Before and after immunization, the immunoglobulin subtypes IgG1, IgG2b, IgG2c, and IgG3 were increased, respectively. IgG2c, corresponding to the IgG1 fraction containing human acetylcholine receptor antibodies, significantly increased.Although a decrease in the acetylcholine receptor alpha1 subunit in the gastrocnemius muscle was observed upon immunization, clinical weakness could be observed.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

このヒト重症筋無力症の病態に関連した動物モデルの作成は医学研究において重要な意義を持つ。マウスにアセチルコリン受容体α1サブユニットに対する抗体を免疫することで、免疫グロブリンの特定のサブタイプの増加やアセチルコリン受容体α1サブユニットの減少が観察された。これはヒト重症筋無力症の病態に関連する特徴的な免疫反応を再現した可能性を示唆する。このような動物モデルの作成と研究は、ヒト重症筋無力症の病態や免疫メカニズムの解明に寄与し、新しい治療法や予防策の開発につながる可能性がある。