ApoE-/- mice |
Targeting the ApoE gene in embryonic stem cells by homologous recombination |
No ApoE present in the blood, hypercholesterolemia, atherosclerotic lesions |
28. Piedrahita JA, Zhang SH, Hagaman JR, Oliver PM, Maeda N. Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. Proc Natl Acad Sci USA 1992; 89: 4471–4475, doi: 10.1073/pnas.89.10.4471. https://doi.org/10.1073/pnas.89.10.4471...
28,3030. Plump AS, Smith JD, Hayek T, Aalto-Setala K, Walsh A, Verstuyft JG, et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 1992; 71: 343–353, doi: 10.1016/0092-8674(92)90362-G. https://doi.org/10.1016/0092-8674(92)903...
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ApoE/LDLr double-knock-out mice |
Crossing of homozygous ApoE knock-out and LDLr knock-out lines |
Demonstrate vascular remodeling and intimal thickening, accelerated atherosclerosis development compared to ApoE single knock-out |
3131. Bonthu S, Heistad DD, Chappell DA, Lamping KG, Faraci FM. Atherosclerosis, vascular remodeling, and impairment of endothelium-dependent relaxation in genetically altered hyperlipidemic mice. Arterioscler Thromb Vasc Biol 1997; 17: 2333–2340, doi: 10.1161/01.ATV.17.11.2333. https://doi.org/10.1161/01.ATV.17.11.233...
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ApoE*3-Leiden mice |
Injection of the DNA fragment into fertilized eggs |
Elevated plasma cholesterol and triglycerides, diet-induced hypercholesterolemia comparable to that in affected humans |
3232. Van den Maagdenberg AM, Hofker MH, Krimpenfort PJ, de Bruijn I, van Vijmen B, van der Boom H, et al. Transgenic mice carrying the apolipoprotein E3-Leiden gene exhibit hyperlipoproteinemia. J Biol Chem 1993; 268: 10540–10545.
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PCSK9 D374Y gain-of-function mutant mice |
Injection of adeno-associated virus (AAV) vector into ApoE-/- mice |
Greatly increased atherosclerotic lesions compared to ApoE knock-out |
33. Bjorklund M, Hollensen AK, Hagensen MK, Dagnaes-Hansen F, Christoffersen C, Mikkelsen JG, et al. Induction of atherosclerosis in mice and hamsters without germline genetic engineering. Circ Res 2014; 114: 1684–1689, doi: 10.1161/CIRCRESAHA.114.302937. https://doi.org/10.1161/CIRCRESAHA.114.3...
33,3434. Roche-Molina M, Sanz-Rosa D, Cruz FM, Garcia-Prieto J, Lopez S, Abia R, et al. Induction of sustained hypercholesterolemia by single adeno-associated virus-mediated gene transfer of mutant hPCSK9. Arterioscler Thromb Vasc Biol 2015; 35: 50–59, doi: 10.1161/ATVBAHA.114.303617. https://doi.org/10.1161/ATVBAHA.114.3036...
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ApoE-/- rabbits |
ZFN, Cas9 techniques |
Increased cholesterol and triglycerides levels, diet-induced hyperlipidemia, atherosclerotic lesions |
36. Ji D, Zhao G, Songstad A, Cui X, Weinstein EJ. Efficient creation of an APOE knockout rabbit. Transgenic Res 2015; 24: 227–235, doi: 10.1007/s11248-014-9834-8. https://doi.org/10.1007/s11248-014-9834-...
36,3737. Yang D, Xu J, Zhu T, Fan J, Lai L, Zhang J, et al. Effective gene targeting in rabbits using RNA-guided Cas9 nucleases. J Mol Cell Biol 2014; 6: 97–99, doi: 10.1093/jmcb/mjt047. https://doi.org/10.1093/jmcb/mjt047...
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LDLr-/- pigs |
Deletion of LDLr in cultured fibroblasts and cloning knock-out embryos |
Rapid development of balloon injury-induced coronary atherosclerosis |
3838. Ogita M, Miyauchi K, Onishi A, Tsuboi S, Wada H, Konishi H, et al. Development of accelerated coronary atherosclerosis model using low density lipoprotein receptor knock-out swine with balloon injury. PLoS One 2016; 11: e0163055, doi: 10.1371/journal.pone.0163055. https://doi.org/10.1371/journal.pone.016...
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