Histological and functional analysis of phosphodesmin-deficient mice

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15615
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Mie University
• Principal Investigator: Yamakawa Daishi 三重大学, 医学系研究科, 助教 (20631097)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 中間径フィラメント / 筋肉 / 心筋 / 骨格筋 / 筋再生 / デスミン

Outline of Final Research Achievements

To understand the physiological significance of mitotic phosphorylation of muscle specific intermediate filament desmin, we generated mitotic desmin phosphorylation defective mice (DES SA/SA mice). Compare to wild type mice, DES SA/SA mice were no difference of appearance. However, in heart muscle tissue, DES SA/SA mice showed decrease of desmin expression in Z band area except intercalated disc. Therefore, we need to clarify heart function in the future. In skeletal muscle tissue, when we induced acute muscle injury by glycerol injection, DES SA/SA mice were injured broadly and delayed muscle regeneration. In future, we will work on solution of detail mechanism with regards to pre-existing muscle tissue homeostasis and abnormal cell division of muscle stem cell which is called satellite cell.

Free Research Field

病態生理学

Academic Significance and Societal Importance of the Research Achievements

デスミンリン酸化の生理的意義を明らかにすることで、細胞同士の融合で多核となる筋組織の形成メカニズムの詳細を知ることができる。これを元に筋組織の老化や障害に対する効率の良い筋肉再生法の開発に貢献することが期待できる。またヒトにおいてもデスミンは遺伝的変異が原因によるミオパチーが存在し、リン酸化部位の変異もいくつか知られている。そのため、デスミンの遺伝子変異によるミオパチーの治療法の開発にも本研究で獲られる知見が役立つと考える。