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Updated: Oct 9, 2025
Production of Apolipoprotein C-III Knockout Rabbits using Zinc Finger Nucleases
Published on: November 18, 2013
CRISPR/Cas9-mediated knockout of APOC3 stabilizes plasma lipids and inhibits atherosclerosis in rabbits
Yiwen Zha1, Yaoyao Lu1, Ting Zhang2
1Medical College, Yangzhou University, Yangzhou, 225001, Jiangsu, China.
Background:
High levels of apolipoprotein C3 (APOC3) can lead to hypertriglyceridemia, which increases the risk of cardiovascular disease. We aim to create APOC3-knockout (KO) rabbits and explore the effects of APOC3 deletion on the occurrence and development of atherosclerosis.
Methods:
An sgRNA anchored to exon 2 of APOC3 was designed to edit embryo genomes using the CRISPR/Cas9 system. The founder rabbits were sequenced, and their lipid profile, inflammatory cytokines, and atherosclerotic plaques were analyzed.
Results:
When given a normal chow (NC) diet, all APOC3-KO rabbits had 50% lower triglyceride (TG) levels than those of the matched age control group. Additionally, their plasma lipoprotein lipase increased. When fed a high-fat diet, APOC3 deficiency was observed to be more conducive to the maintenance of plasma TG, total cholesterol, and low-density lipoprotein cholesterol levels, and the inhibition of the inflammatory response and the protection against atherosclerosis in rabbits.
Conclusion:
APOC3 deficiency can delay the formation of atherosclerosis-induced HFD in rabbits, indicating this is a novel therapeutic target to treat atherosclerosis.
Insights
Apolipoprotein C3 (APOC3) knockout rabbits show significantly lower triglyceride levels and reduced atherosclerosis. APOC3 deficiency offers protection against high-fat diet-induced cardiovascular disease.
Area of Science:
- Genetics and Molecular Biology
- Cardiovascular Research
- Metabolic Disease
Background:
- High apolipoprotein C3 (APOC3) levels are linked to hypertriglyceridemia and increased cardiovascular disease risk.
- Atherosclerosis development is a significant concern in cardiovascular pathology.
Purpose of the Study:
- To generate apolipoprotein C3 (APOC3)-knockout rabbits using CRISPR/Cas9 technology.
- To investigate the impact of APOC3 deletion on hypertriglyceridemia and atherosclerosis progression.
Main Methods:
- CRISPR/Cas9 system utilized for genome editing of APOC3 in rabbit embryos.
- Analysis of lipid profiles, inflammatory cytokines, and atherosclerotic plaque formation in APOC3-knockout rabbits.
Main Results:
- APOC3-knockout rabbits exhibited a 50% reduction in triglyceride levels on a normal chow diet.
- APOC3 deficiency improved lipid profiles, reduced inflammation, and protected against atherosclerosis under high-fat diet conditions.
Conclusions:
- APOC3 deficiency delays the formation of atherosclerosis, particularly in response to a high-fat diet.
- APOC3 presents a potential novel therapeutic target for treating atherosclerosis.
