仓鼠在脂代谢方面与大小鼠不同，胆固醇酯转运蛋白（CETP）高表达，肝脏没有载脂蛋白B48编辑活性，而与人类高度相似。因此血浆脂蛋白谱、对高脂饲料的反应也均与人类相同，是人类心血管疾病的极佳动物模型。然而因为技术难题，基因工程仓鼠直到去年才由本研究组率先研发成功。目前我们又制备了低密度脂蛋白受体敲除（LDLR KO）仓鼠，杂合子及纯合子的血浆胆固醇不需要喂饲高脂饲料就增高50%和4倍，与人类家族性高胆固醇血症相似。本项目拟以此为基础，建立类人化动脉粥样硬化（As）小动物模型。我们将系统地比较大、小鼠和仓鼠三种动物的LDLR KO模型，确认仓鼠的表型特点和优势，引入环境因素建立冠心病小动物模型，并明确LDLR KO仓鼠在抗As新药研发上的应用价值。本项目的实施将建立类人化小型心血管疾病动物模型，为不适合使用大小鼠的研究提供新的模式动物平台，开创和引领一个类人化的小型心血管疾病动物模型新领域。

Hamster is different in lipid metabolism with mouse and rat, such as cholesteryl ester transfer protein (CETP) highly expressed, liver without apolipoprotein B48 editing activity. These features are highly similar to human being. Therefore, hamster has the same plasma lipoprotein profile and response to high-fat diet with humans. Hamster is an excellent animal model for human cardiovascular disease. However, because of technical problems, our group was the first to develop genetic engineering hamster model successfully until last year. Then we prepared subsequently the LDL receptor knockout (LDLR KO) hamsters. The homozygous and heterozygous plasma cholesterol increased 4 times and 50% without high fat high cholesterol diets, so that the phenotype of the model is consistent with human familial hypercholesterolemia. This project aims to take this as a basis to establish the man-like atherosclerosis (As) small animal models. We will systematically compare three LDLR KO models of mice, rats and hamsters to confirm the phenotypic characteristics and advantages of hamsters. And we will establish a small animal model of coronary heart disease by the introduction of environmental factors. We will also make it clear LDLR KO hamsters have the value of application in anti-As new drug development. The implementation of this project will establish man-like cardiovascular disease small animal models to provide a new platform of animal model for the studies not suitable using rats and mice. And it will creat and lead a new study field of man-like cardiovascular disease small animal models.