构建ApoC2基因敲除的类人化仓鼠模型探讨高甘油三酯血症与动脉粥样硬化关系

项目名称： 构建ApoC2基因敲除的类人化仓鼠模型探讨高甘油三酯血症与动脉粥样硬化关系

项目编号： No.31670816

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 李向平

作者单位： 中南大学

项目金额： 25万元

中文摘要： 高甘油三酯血症（HTG）是动脉粥样硬化（AS）的独立危险因素，但其机制不明。载脂蛋白C2（ApoC2）作为分解血中富含甘油三酯（TG）脂蛋白的关键酶脂蛋白脂酶的激活物，是血浆TG水平的重要调控因子。通过敲除ApoC2基因建立类人化的HTG动物模型，进行HTG相关的AS发病机制及其干预措施的研究具有重要意义。ApoC2基因敲除小鼠新近才有报道，该小鼠造成的HTG对AS有何种影响还完全未知。小鼠与人类脂代谢的差异巨大，而仓鼠脂代谢及AS易感性与人类高度近似，后者是研究心血管疾病的理想动物。我们已率先在国际上构建了第一个基因工程仓鼠模型，拟进一步应用CRISPR/Cas9技术构建ApoC2基因敲除的类人化仓鼠模型，并利用这种完全自主知识产权的模型探讨HTG相关AS的病理机制研究。本项目不但为HTG相关AS的研究提供理想的平台，而且可为AS相关疾病的防治提供新理论和新思路。

中文关键词： 高甘油三酯血症；动脉粥样硬化；载脂蛋白C2；仓鼠

英文摘要： Hypertriglyceridemia (HTG) is an independent risk factor for atherosclerosis (AS), but the underlying mechanisms are not clear. As an activator of lipoprotein lipase that is the key enzyme in the intravascular hydrolysis of triglyceride-rich lipoproteins, apolipoprotein C2 (ApoC2) is an essential regulator of the plasma TG levels. Establishing the humanoid HTG animal models by ApoC2 knock-out and investigating the pathogenesis about HTG-related AS and conducting intervention studies in them have very important significance. Recently, the ApoC2 knock-out mice have been reported, but it is totally unknown how ApoC2 knock-out induced HTG in mice affects AS. There are many differences in lipid metabolism between mouse and human, while hamster is quite similar to human in lipid metabolism and susceptible to AS. Thus, the latter is an optimal animal model for the cardiovascular disease studies. We were the first to establish the genetic engineering hamster model in the world and intend to further build ApoC2 knock-out humanoid hamster model by CRISPR/Cas9 technique. Moreover, we will investigate the pathological mechanism of HTG-related AS by using the hamster model that possesses China's independent intellectual property rights. This project will not only provide an ideal platform for the researches of HTG-related AS, but also present new theories and new ideas for the prevention and treatment of AS-related diseases.

英文关键词： Hypertriglyceridemia ;Atherosclerosis; Apolipoprotein C2 ;Hamster