Clarification of novel functions of the protein degradation system

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19568
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Pathology, Infection/Immunology, and related fields
• Research Institution: Wakayama Medical University
• Principal Investigator: Kaisho Tsuneyasu 和歌山県立医科大学, 先端医学研究所, 教授 (60224325)
• Co-Investigator(Kenkyū-buntansha): 金澤 伸雄 和歌山県立医科大学, 医学部, 准教授 (90343227)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 炎症 / タンパク質分解 / 免疫プロテアソーム / 遺伝子変異

Outline of Final Research Achievements

Proteasome is a protein complex and involved in cell or individual homeostasis by degrading unnecessary proteins. Genetic mutation of a proteasome subunit leads to refractory inflammations, called autoinflammatory diseases, but the underlying pathological mechanisms remain largely unknown. We have generated mutant mice carrying a novel genetic mutation of a proteasome subunit, which was found in an autoinflammatory patient and found multiple immune disorders in the mutant mice. The mutant mice are novel and quite useful for clarifying the pathogenesis of autoinflammatory diseases.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

単一遺伝子の変異によって難治性の炎症病態を来す自己炎症性疾患の病態を明らかにすることは、当該疾患ばかりでなく、がんや炎症など一般的な炎症病態の治療法の開発にも有用である。本研究では、自己炎症性疾患患者由来の新規の遺伝子変異を持つマウスを作成し、その変異が多彩な免疫異常をきたすユニークな表現型を呈することを明らかにした。この変異マウスの解析を進めることにより、炎症病態の新たなメカニズムを明らかになり、新規の炎症制御剤の開発に結び付く成果が期待される。