Knockout rat models mimicking human atherosclerosis created by Cpf1-mediated gene targeting

Scientific Reports
Jong Geol LeeIn-Jeoung Baek

Abstract

The rat is a time-honored traditional experimental model animal, but its use is limited due to the difficulty of genetic modification. Although engineered endonucleases enable us to manipulate the rat genome, it is not known whether the newly identified endonuclease Cpf1 system is applicable to rats. Here we report the first application of CRISPR-Cpf1 in rats and investigate whether Apoe knockout rat can be used as an atherosclerosis model. We generated Apoe- and/or Ldlr-deficient rats via CRISPR-Cpf1 system, characterized by high efficiency, successful germline transmission, multiple gene targeting capacity, and minimal off-target effect. The resulting Apoe knockout rats displayed hyperlipidemia and aortic lesions. In partially ligated carotid arteries of rats and mice fed with high-fat diet, in contrast to Apoe knockout mice showing atherosclerotic lesions, Apoe knockout rats showed only adventitial immune infiltrates comprising T lymphocytes and mainly macrophages with no plaque. In addition, adventitial macrophage progenitor cells (AMPCs) were more abundant in Apoe knockout rats than in mice. Our data suggest that the Cpf1 system can target single or multiple genes efficiently and specifically in rats with genetic heritabil...Continue Reading

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Citations

Sep 5, 2019·Transgenic Research·Charles-Etienne DumeauAnton Wutz
Aug 13, 2020·International Journal of Experimental Pathology·Siân P CartlandMary M Kavurma
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Dec 25, 2021·Nucleic Acids Research·Bijoya PaulGuillermo Montoya

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Methods Mentioned

BETA
gene knockout
genotyping
biopsies
targeted mutations
electrophoresis
PCR
Fluorescence

Software Mentioned

Image J
Benchling

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