Elucidation of the role of epigenetic regulation by NRSF complex in maintaining cardiac integrity

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860596
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kyoto University
• Principal Investigator: KUWABARA Yoshihiro 京都大学, 医学(系)研究科(研究院), 研究員 (40647400)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 転写因子 / NRSF / 心不全 / エピゲノム / 循環器

Outline of Final Research Achievements

In this study, I succeeded to generate cardiac-specific NRSF conditional knockout mice (NRSF ccKO) and found that these mice show cardiac dysfunction, malignant arrhythmias and sudden cardiac death, implying that NRSF plays an essential role in maintaining normal cardiac function. To address the underlying mechanisms, I crossed these mice with HDAC1/2 cardiac-specific double heterozygote knockout mice and analyzed NRSF/HDAC1/2 cardiac-specific triple heterozygote knockout mice. I also found that GNAO1 gene expression is increased in NRSF ccKO. To examine the contribution of G alpha O to cardiac dysfunction seen in NRSF ccKO, I treated these mice with PTX and found that PTX improved cardiac function and the survival curve in NRSF ccKO. Currently I am further analyzing the role of G alpha O in the phenotype of NRSF ccKO.

Free Research Field

循環器内科