Molecular mechanism in cardiomyopathy patients with DSC2 mutation

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15890
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Yamaguchi University
• Principal Investigator: FUKUDA Masakazu 山口大学, 医学部附属病院, 診療助教(4日/週) (30815668)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: デスモコリン / デスモゾーム

Outline of Final Research Achievements

We succeeded in creating, breeding and genotyping DSC2 (G790Δ) KI mice. DSC2 (G790Δ) KI mice were electrocardiogram and echocardiographically. In addition, VT induction test and exercise test were performed. However, no significant increase in arrhythmia was observed in DSC2 (G790Δ) KI mice. Fluorescent immunostaining showed no significant changes in the staining of various desmosome-related proteins including DSC2. Echocardiographic measurements revealed that DSC2 KI mice had mild dilation and reduced contractility, especially in homozygous mice.
In DSC2 (G790Δ) KI mice, a slight decrease in cell shortening was observed in homozygous mice.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

DSC2 KIマウスを世界で初めて作成し、論文化できたことは学術的意義があったが、当初仮説を立てていたDSC2変異における催不整脈性や（可逆的な）細胞内Ca2+ハンドリング異常を誘導する可能性についてはnegativeなデータであった。