ApoE-/-或LDLR-/-小鼠模型为人类对动脉粥样硬化（AS）的认识提供了强有力的工具，但其体内脂质代谢和斑块的转归与人类有较大的差别，导致部分临床医学转化的失败。仓鼠在血液细胞成分和血脂代谢方面与人类高度相似，血浆脂蛋白谱、对高脂饲料的反应也均与人类相同，有望成为更为理想的动脉粥样硬化血栓和抗血栓新药研究的新型疾病动物模型。本项目将利用合作单位采用CRISPRE/Cas9技术构建的类人化低密度脂蛋白受体敲除（LDLR KO）的仓鼠，结合申请者在血栓研究领域的优势，规范的建立仓鼠血液分析方法和血栓模型。并对比传统的小鼠血栓模型，全面的分析类人化模式动物仓鼠作为血栓研究的优势和在筛选抗凝血和抗血小板新药方面的应用价值。

ApoE-/- and LDLR-/- mice models provide powerful tools for understanding the mechanisms of atherosclerosis (AS) in human. However, due to considerable differences in lipid metabolism and plaque formation between mice and human, only a few clinical trials succeed in recapitulating the benefits of novel drugs observed from basic studies. In the search of revolutionary model animals with more resemblance to human, hamsters stand out as a favorable option. Previous studies showed that hamsters harbor similar hemocyte components, lipid metabolism, plasma lipoprotein spectrum, as well as high-fat feed response in regard to human, thus providing an ideal animal model for studying atherothrombosis and antithrombotic agents in translational medicine. Previously, our collaborators generated a low density lipoprotein receptor knockout (LDLR-/-) hamster strain using the CRISPRE/Cas9 platform. Next, we will establish animal surgical models of thrombosis and protocols of blood analysis utilizing the genetically modified hamsters. By systematically comparing the characteristics of hemostasis and thrombosis between mice and hamsters, we will further evaluate the efficacy of hamsters in the study of thrombosis and screening of novel anticoagulant and antiplatelet drugs.