Analysis of Psmb8 mutation-transgenic mice, model of Nakajo-Nishimura syndrome

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08780
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Inaba Yutaka 和歌山県立医科大学, 医学部, 講師 (00647571)
• Co-Investigator(Kenkyū-buntansha): 金澤 伸雄 兵庫医科大学, 医学部, 教授 (90343227) ; 国本 佳代 和歌山県立医科大学, 医学部, 講師 (10438278) ; 三木田 直哉 和歌山県立医科大学, 医学部, 博士研究員 (60405462)
• Project Period (FY): 2020-03-01 – 2023-03-31
• Keywords: 中條西村症候群 / 自己炎症性疾患 / Psmb8 / プロテアソーム / 脂肪萎縮 / 早老症

Outline of Final Research Achievements

Nakajo-Nishimura syndrome is a condition clinically similar to progeria, characterized by lipoatrophy that leads to emaciation and premature death. It is a unique hereditary inflammatory and wasting disease, and was registered as a designated incurable disease in 2011 as a hereditary autoinflammatory disease.
The disease's etiology involves a dysfunction of proteasomes, which are responsible for breaking down unnecessary proteins, although the exact mechanism remains unknown. In this study, we created a mouse model of Nakajo-Nishimura syndrome to elucidate the pathogenesis of the disease.
The mice exhibited decreased survival, lipoatrophy and abnormal immunocompetence, mirroring the characteristics of Nakajo-Nishimura syndrome. Currently, there is no known treatment for this short-lived disease. However, the utilization of this mouse model holds the potential for future advancements in developing treatments for Nakajo-Nishimura syndrome.

Free Research Field

自己炎症性疾患

Academic Significance and Societal Importance of the Research Achievements

中條-西村症候群のモデルマウスを作成し、ヒトと同様に生存率の低下、脂肪萎縮、免疫能に異常を認めることがわかった。
本疾患はプロテアソームの機能不全であり、本マウスを解析することにより中條-西村症候群の病因解明、治療法の開発に寄与するのは、もちろんであるがプロテアソームの機能自体を解明できる可能性もある。中條-西村症候群のみではなく、プロテアソームが関連する疾患の解明にも貢献する社会的にも学術的にも大きな成果となった。