ArticleLipids in health and disease2019
Generation of hyperlipidemic rabbit models using multiple sgRNAs targeted CRISPR/Cas9 gene editing system.
Article in Lipids in health and disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Preclinical techniques to investigate exercise training in vascular pathophysiology.American journal of physiology. Heart and circulatory physiology · 2021Pooled it
- Efficient Microinjection and CRISPR/Cas9 Mediated Genome Editing in Urechis unicinctus.Marine biotechnology (New York, N.Y.) · 2026Article
- Multimodal retinal imaging evaluation of macular degeneration persistent disease activity animal model in Watanabe heritable hyperlipidemic rabbits.Experimental eye research · 2025Article
- Genome-edited rabbits: Unleashing the potential of a promising experimental animal model across diverse diseases.Zoological research · 2024Review
- Applications of Genome Editing Technologies in CAD Research and Therapy with a Focus on Atherosclerosis.International journal of molecular sciences · 2023Review
- Genome Editing in Dyslipidemia and Atherosclerosis.Advances in experimental medicine and biology · 2023Review
- Emerging degrader technologies engaging lysosomal pathways.Chemical Society reviews · 2022Review
- Non-Mouse Models of Atherosclerosis: Approaches to Exploring the Translational Potential of New Therapies.International journal of molecular sciences · 2022Review
- Targeted Elimination ofInfection and drug resistance · 2022Article
- CRISPR/Cas9-mediated knockout of APOC3 stabilizes plasma lipids and inhibits atherosclerosis in rabbits.Lipids in health and disease · 2021Article
- Degradation of lipid droplets by chimeric autophagy-tethering compounds.Cell research · 2021Article
- Harnessing the Potential of CRISPR/Cas in Atherosclerosis: Disease Modeling and Therapeutic Applications.International journal of molecular sciences · 2021Review
- Alcohol Drinking, Apolipoprotein Polymorphisms and the Risk of Cardiovascular Diseases.Current neurovascular research · 2021Review
- Gene Editing in Rabbits: Unique Opportunities for Translational Biomedical Research.Frontiers in genetics · 2021Review
- Generation of mouse conditional knockout alleles in one step using theGenome research · 2021Article
- Nucleic Acid-Based Therapies for Atherosclerosis.Current atherosclerosis reports · 2020Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveTo generate novel rabbit models with a large-fragment deletion of either LDL receptor (LDLR) and/or apolipoprotein (apoE) genes for the study of hyperlipidemic and atherosclerosis.
methodsCRISPR/Cas9 system directed by a multiple sgRNAs system was used in rabbit embryos to edit their LDLR and apoE genes. The LDLR and apoE genes of founder rabbits were sequenced, and their plasma lipids and lipoprotein profiles on a normal chow diet were analyzed, western blotting was also performed to evaluate the expression of apolipoprotein. Sudan IV and HE staining of aortic were performed to confirm the formation of atherosclerosis.
resultsSix knockout (KO) rabbits by injection of both LDLR and apoE sgRNAs were obtained, including four LDLR KO rabbits and two LDLR/apoE double- KO rabbits. Sequence analysis of these KO rabbits revealed that they contained multiple mutations including indels, deletions, and substitutions, as well as two rabbit lines containing biallelic large fragment deletion in the LDLR region. Analysis of their plasma lipids and lipoprotein profiles of these rabbits fed on a normal chow diet revealed that all of these KO rabbits exhibited remarkable hyperlipidemia with total cholesterol levels increased by up to 10-fold over those of wild-type rabbits. Pathological examinations of two founder rabbits showed that KO rabbits developed prominent aortic and coronary atherosclerosis.
conclusionLarge fragment deletions can be achieved in rabbits using Cas9 mRNA and multiple sgRNAs. LDLR KO along with LDLR/apoE double KO rabbits should provide a novel means for translational investigations of human hyperlipidemia and atherosclerosis.
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