RGD Reference Report - Knockout rat models mimicking human atherosclerosis created by Cpf1-mediated gene targeting. - Rat Genome Database

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

Authors: Lee, Jong Geol  Ha, Chang Hoon  Yoon, Bohyun  Cheong, Seung-A  Kim, Globinna  Lee, Doo Jae  Woo, Dong-Cheol  Kim, Young-Hak  Nam, Sang-Yoon  Lee, Sang-Wook  Sung, Young Hoon  Baek, In-Jeoung 
Citation: Lee JG, etal., Sci Rep. 2019 Feb 22;9(1):2628. doi: 10.1038/s41598-019-38732-2.
RGD ID: 150521536
Pubmed: PMID:30796231   (View Abstract at PubMed)
PMCID: PMC6385241   (View Article at PubMed Central)
DOI: DOI:10.1038/s41598-019-38732-2   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ApoeRatatherosclerosis  IMP  RGD 
APOEHumanfamilial hyperlipidemia  ISOApoe (Rattus norvegicus) RGD 
ApoeRatfamilial hyperlipidemia  IMP  RGD 
ApoeMousefamilial hyperlipidemia  ISOApoe (Rattus norvegicus) RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ApoeRatdecreased circulating HDL cholesterol level  IMP  RGD 
ApoeRatincreased circulating cholesterol level  IMP  RGD 
ApoeRatincreased circulating LDL cholesterol level  IMP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Apoe  (apolipoprotein E)

Genes (Mus musculus)
Apoe  (apolipoprotein E)

Genes (Homo sapiens)
APOE  (apolipoprotein E)

Additional Information