期刊
ONCOTARGET
卷 8, 期 23, 页码 37751-37760出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.17154
关键词
cardiovascular disease; dyslipidemia; animal model; multiple-gene knockout; gene editing
资金
- Major National Scientific Research Projects [2015CB943101]
- National Science and Technology Major Project [2016ZX08010004]
- International Advanced Agricultural Science and Technology Import Program [2016-X36]
- Agricultural Science and Technology Innovation Program of CAAS [ASTIP-IAS05]
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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