Elucidating the pathophysiology of inherited aortic diseases by combinational approach of genetic diagnosis and biotechnologies

2016 Fiscal Year Final Research Report

• Project/Area Number: 25461084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Jichi Medical University
• Principal Investigator: Yasushi Imai 自治医科大学, 医学部, 准教授 (20359631)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: マルファン症候群 / 家族性疾患 / 大動脈解離 / 大動脈瘤 / 機能解析 / 遺伝子改変動物

Outline of Final Research Achievements

Marfan syndrome is characterized by clinical manifestations including skeletal abnormalities, ectopia lentis, and aortic dissection / dilatation. We have been followed patients suffering from Marfan syndrome and familial aortic diseases in our facilities and tested their genetic backgrounds by candidate gene approach. Among them, we encountered one pedigree, in which three women among the six siblings suffered from aortic dissection. We detected a novel mutation: MYH11 c3766_3768 del AAG, pK1256del in this pedigree. To elucidate molecular/functional mechanism in this mutation, we established the knock-in mice which carried the aforementioned mutation by new gene editing technology Crisper-Cas 9 system. This knock-in mice have been found to mimic human phenotypes and we have continued further analyses.

Free Research Field

循環器疾患