Spontaneous severe hypercholesterolemia and atherosclerosis lesions in rabbits with deficiency of low-density lipoprotein receptor (LDLR) on exon 7

EBioMedicine
Rui LuYong Cheng

Abstract

Rabbits (Oryctolagus cuniculus) have been the very frequently used as animal models in the study of human lipid metabolism and atherosclerosis, because they have similar lipoprotein metabolism to humans. Most of hyperlipidemia and atherosclerosis rabbit models are produced by feeding rabbits a high-cholesterol diet. Gene editing or knockout (KO) offered another means of producing rabbit models for study of the metabolism of lipids and lipoproteins. Even so, apolipoprotein (Apo)E KO rabbits must be fed a high-cholesterol diet to induce hyperlipidemia. In this study, we used the CRISPR/Cas9 system anchored exon 7 of low-density lipoprotein receptor (LDLR) in an attempt to generate KO rabbits. We designed two sgRNA sequences located in E7:g.7055-7074 and E7:g.7102-7124 of rabbit LDLR gene, respectively. Seven LDLR-KO founder rabbits were generated, and all of them contained biallelic modifications. Various mutational LDLR amino acid sequences of the 7 founder rabbits were subjected to tertiary structure modeling with SWISS-MODEL, and results showed that the structure of EGF-A domain of each protein differs from the wild-type. All the founder rabbits spontaneously developed hypercholesterolemia and atherosclerosis on a normal chow ...Continue Reading

References

Apr 4, 1986·Science·M S Brown, J L Goldstein
May 1, 1994·The Journal of Clinical Investigation·S IshibashiD K Burns
Mar 30, 2002·Nature Biotechnology·Patrick ChesnéJean-Paul Renard
May 10, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Masashi ShiomiJianglin Fan
Jan 12, 2007·Trends in Biochemical Sciences·Jay D HortonHelen H Hobbs
May 15, 2007·Current Opinion in Lipidology·Gilles Lambert
Feb 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Hyock Joo KwonJohann Deisenhofer
Dec 8, 2010·Bioinformatics·Pascal BenkertTorsten Schwede
May 27, 2011·Journal of Clinical Lipidology·Anne C GoldbergUNKNOWN National Lipid Association Expert Panel on Familial Hypercholesterolemia
Dec 14, 2011·Molecular Biology Reports·Małgorzata Waluś-MiarkaDanuta Czarnecka
Mar 9, 2012·Atherosclerosis·Frederick J Raal, Raul D Santos
May 2, 2014·Nucleic Acids Research·Marco BiasiniTorsten Schwede
Sep 14, 2014·Transgenic Research·Diana JiEdward J Weinstein
Aug 9, 2015·Nucleic Acids Research·Blake CarringtonRaman Sood
Jan 3, 2016·Atherosclerosis·Manabu NiimiJianglin Fan
Jun 2, 2016·The Lancet. Diabetes & Endocrinology·Raul D SantosUNKNOWN International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel
May 5, 2017·JCI Insight·Srinivas D SithuSanjay Srivastava
May 6, 2017·Investigative Ophthalmology & Visual Science·Lin YuanLiangxue Lai
May 10, 2017·European Journal of Pharmacology·Besa Emini VeseliGuido R Y De Meyer

❮ Previous
Next ❯

Citations

Nov 27, 2019·British Journal of Pharmacology·Ioanna AndreadouPéter Ferdinandy
May 1, 2020·Expert Opinion on Investigational Drugs·Tycho R TrompG Kees Hovingh
Apr 30, 2019·Frontiers in Cardiovascular Medicine·Sara OppiSokrates Stein
Jul 28, 2020·Frontiers in Cardiovascular Medicine·Viviana L VedderJeanette Erdmann
Mar 21, 2019·Current Opinion in Lipidology·Mia Furgurson, William R Lagor
Jan 2, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Gurneet S SanghaAlisa M Clyne
Feb 20, 2021·Frontiers in Genetics·Jianglin FanY Eugene Chen
Jul 23, 2021·Food & Function·Roberto Martínez-BeamonteJesús Osada
Aug 28, 2021·International Journal of Molecular Sciences·Wei Sheng SiewWei Hsum Yap

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsy
PCR
electrophoresis
ELISA

Software Mentioned

MODEL
SWISS
[UNK]
Image
Pro [UNK]
Pro

Related Concepts

Related Feeds

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.