ApoE knockout rabbits: A novel model for the study of human hyperlipidemia
ApoE knockout rabbits: A novel model for the study of human hyperlipidemia
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DOI：
10.1016/j.atherosclerosis.2015.12.002
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发表时间：
2016-02-01
期刊：
影响因子：
5.3
通讯作者：
Fan, Jianglin
中科院分区：
文献类型：
--
作者：
Niimi, Manabu;Yang, Dongshan;Fan, Jianglin
目的：兔是研究高脂血症和动脉粥样硬化的最佳动物模型之一。虽然已经创造了许多转基因兔，但由于缺乏兔胚胎干细胞，基因敲除(KO)兔的发育一直是不可能的。我们和其他人最近使用基因组编辑技术培育了KO兔。在本研究中，我们研究了饮食和胆固醇饮食下apoE KO兔的脂蛋白谱，并研究了它们对饮食诱导的动脉粥样硬化的易感性。方法和结果：我们分析了apoE KO兔的血脂和脂蛋白，并将其与野生型兔进行了比较。在饲料中，纯合子(但不是杂合子)apoE KO兔表现出轻微的高脂血症，当被胆固醇饮食激发时，它们比野生型兔更容易发生饮食诱导的高脂血症，它们的血浆总胆固醇水平显著升高(apoE KO组为1070+/-61 mg/dL，野生型为169+/-79 mg/dL，p<；0.001)。ApoE KO兔的高脂血症是由残余脂蛋白升高引起的。有趣的是，apoE KO兔体内残留脂蛋白的增加以apoB-48为主，并富含apoA-I和apoA-IV。此外，高脂饲料喂养10周后，ApoE KO兔的动脉粥样硬化程度明显高于野生型。结论：本研究首次报道了可用于脂类和脂蛋白代谢研究的ApoE KO兔。APOE KO兔是研究人类高脂血症和动脉粥样硬化的有用模型。(C)2015爱思唯尔爱尔兰有限公司。保留所有权利。
Objective: Rabbits are one of the best animal models for the study of hyperlipidemia and atherosclerosis. Although many transgenic rabbits have been created, the development of gene knockout (KO) rabbits has been impossible due to the lack of rabbit embryonic stem cells. We along with others recently generated KO rabbits using genome editing techniques. In the current study, we characterized the lipoprotein profiles of apoE KO rabbits on both chow and cholesterol diets and investigated their susceptibility to a diet-induced atherosclerosis.Approach and results: We analyzed plasma lipids and lipoproteins of apoE KO rabbits and compared them with those of wild-type rabbits. On a chow diet, homozygous (but not heterozygous) apoE KO rabbits showed mild hyperlipidemia and, when challenged with a cholesterol diet, they showed greater susceptibility to diet-induced hyperlipidemia than did the wild-type rabbits and their plasma total cholesterol levels were remarkably increased (1070 +/- 61 mg/dL in apoE KO vs. 169 +/- 79 mg/dL in the wild type, p< 0.001). Hyperlipidemia in apoE KO rabbits was caused by elevated remnant lipoproteins. Interestingly, increased remnant lipoproteins in apoE KO rabbits were predominated by apoB-48 and rich in both apoA-I and apoA-IV contents. Furthermore, apoE KO rabbits developed greater aortic atherosclerosis than wild-type rabbits when fed with a cholesterol diet for 10 weeks.Conclusions: To our knowledge, this is the first report of generating KO rabbits for the study of lipid and lipoprotein metabolism. ApoE KO rabbits should be a useful model for the study of human hyperlipidemia and atherosclerosis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.