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

2015 Fiscal Year Final Research Report

• Project/Area Number: 25670190
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: University of Yamanashi
• Principal Investigator: FAN Jianglin 山梨大学, 総合研究部, 教授 (60272192)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 遺伝子改変ウサギ / 動脈硬化 / ノックアウト

Outline of Final Research Achievements

In this project, we attempted to create knock-out and knock-in rabbit models using TALEN and CRISPR-Cas9 methods. We first generated apoE KO rabbits using CRISPR-Cas9 and obtained two founders. After several breeding, we were able to get both heterozygous and homozygous apoE KO rabbits. Compared with wild-type rabbits, chow-fed apoE KO rabbits exhibited high levels of plasma total cholesterol and triglycerides with no changes in HDL-C levels. When these rabbits were fed with a diet containing a 0.3% cholesterol for 2 weeks, apoE KO showed more prominent hyperlipidemia than wild-type rabbits with increased plasma remnant lipoproteins and apoB48 contents. These rabbits also showed more aortic atherosclerosis than wild-type rabbits. These apoE KO rabbits should become a useful model for the study of human type III hyperlipidemia. We also created apoAII knock-in rabbits and are in the process of breeding and characterization.

Free Research Field

分子病理学