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Knockout rat models mimicking human atherosclerosis created by Cpf1-mediated gene targeting
- Source :
- Scientific Reports, Scientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group UK, 2019.
-
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 heritability and that Apoe knockout rats may help understand initial-stage atherosclerosis.
- Subjects :
- 0301 basic medicine
Apolipoprotein E
Knockout rat
lcsh:Medicine
Biology
Article
Rats, Sprague-Dawley
03 medical and health sciences
Gene Knockout Techniques
0302 clinical medicine
Immune system
Apolipoproteins E
Hyperlipidemia
medicine
Macrophage
Animals
Progenitor cell
lcsh:Science
Multidisciplinary
Base Sequence
lcsh:R
Gene targeting
medicine.disease
Atherosclerosis
Endonucleases
Cell biology
Disease Models, Animal
030104 developmental biology
Receptors, LDL
Knockout mouse
Gene Targeting
Mutation
lcsh:Q
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....70aaeecaa08c52053434580d7bbb8dbe