Creation of Knock-out rabbit models for the study of atherosclerosis

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H04718
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: University of Yamanashi
• Principal Investigator: FAN Jianglin 山梨大学, 大学院総合研究部, 教授 (60272192)
• Co-Investigator(Kenkyū-buntansha): 北嶋 修司 佐賀大学, 総合分析実験センター, 准教授 (70284643)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: リポ蛋白代謝 / 高脂血症 / 動脈硬化 / 動物モデル

Outline of Final Research Achievements

Apolipoprotein CIII (apoCIII) is a constituent of all lipoproteins except LDLs and mediates the metabolism of triglyceride (TG)-rich lipoproteins through inhibition of LPL activity. Elevated plasma levels of apoCIII are directly correlated with the plasma TG and increase the cardiovascular risk. However, the pathophysiological functions of apoCIII in vivo have not been fully elucidated. To examine the functional roles of apoCIII in lipoprotein metabolism and atherosclerosis, we generated both trangesgenic (Tg) and apoCIII knockout (KO) rabbits. Tg rabbits showed high levels of plasma TG whereas apoCIII KO rabbits exhibited lower plasma levels of TG than those of wild-type (WT) rabbits while total cholesterol and HDL-cholesterol levels were unchanged. Analysis of lipoproteins revealed that reduced plasma TG levels in KO rabbits were accompanied by significant reduction of VLDLs and intermediate-density lipoproteins (IDLs).

Free Research Field

基礎医学

Academic Significance and Societal Importance of the Research Achievements

動脈硬化とその合併症である心筋梗塞、脳卒中といった疾患は、日本を始めとした先進国における死亡原因の約30%を占め、人口の高齢化が加速する中で、今や医学領域のみならず社会経済的にも最も重要な課題となっている。新規アポCIII遺伝子改変ウサギモデルの確立は、動脈硬化の研究に限らず、脂質代謝、高脂血症の研究及び新薬の開発に新たな研究ツールとしての利用が期待される。