CRISPR/Cas9-mediated ApoE(-/-) and LDLR-/- double gene knockout in pigs elevates serum LDL-C and TC levels

文献类型： 外文期刊

第一作者： Huang, Lei

作者： Huang, Lei;Cheng, Ying;Xu, Kui;Gao, Qian;Xia, Ying;Liu, Yang;Zhang, Xue;Mu, Yulian;Li, Kui;Hua, Zaidong;Xiao, Hongwei;Zheng, Xinming;Huang, Lei

作者机构：

关键词： cardiovascular disease;dyslipidemia;animal model;multiple-gene knockout;gene editing

期刊名称：ONCOTARGET （ 影响因子：5.168； 五年影响因子：5.312 ）

ISSN： 1949-2553

年卷期： 2017 年 8 卷 23 期

页码：

收录情况： SCI

摘要： The traditional method to establish a cardiovascular disease model induced by high fat and high cholesterol diets is time consuming and laborious and may not be appropriate in all circumstances. A suitable pig model to study metabolic disorders and subsequent atherosclerosis is not currently available. For this purpose, we applied the CRISPR/Cas9 system to Bama minipigs, targeting apolipoprotein E (ApoE) and low density lipoprotein receptor (LDLR) gene simultaneously. Six biallelic knockout pigs of these two genes were obtained successfully in a single step. No off-target incidents or mosaic mutations were detected by an unbiased analysis. Serum biochemical analyses of gene-modified piglets showed that the levels of low density lipoprotein choleserol (LDL-C), total cholesterol (TC) and apolipoprotein B (APOB) were elevated significantly. This model should prove valuable for the study of human cardiovascular disease and related translational research.

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