ArticleLipids in health and disease2020
Hyperhomocysteinemia and dyslipidemia in point mutation G307S of cystathionine β-synthase-deficient rabbit generated using CRISPR/Cas9.
Article in Lipids in health and disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 8 citations in OpenAlex.
- Linking homocysteine and ferroptosis in cardiovascular disease: insights and implications.Apoptosis : an international journal on programmed cell death · 2024Review
- Catalpol inhibits HHcy-induced EndMT in endothelial cells by modulating ROS/NF-κB signaling.BMC cardiovascular disorders · 2024Article
- Hydrogen sulphide in liver glucose/lipid metabolism and non-alcoholic fatty liver disease.European journal of clinical investigation · 2022Review
- Mechanism of homocysteine-mediated endothelial injury and its consequences for atherosclerosis.Frontiers in cardiovascular medicine · 2022Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundCongenital hyper-homocysteinemia (HHcy) is caused by a defective cystathionine β-synthase (CBS) gene, and is frequently associated with dyslipdemia. The aim of this study was to further elucidate the effect of mutated CBS gene on circulating lipids using a rabbit model harboring a homozygous G307S point mutation in CBS.
methodsCRISPR/Cas9 system was used to edit the CBS gene in rabbit embryos. The founder rabbits were sequenced, and their plasma homocysteine (Hcy) and lipid profile were analyzed.
resultsSix CBS-knockout (CBS-KO) founder lines with biallelic modifications were obtained. Mutation in CBS caused significant growth retardation and high mortality rates within 6 weeks after birth. In addition, the 6-week old CBS-KO rabbits showed higher plasma levels of Hcy, triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared to the age-matched wild-type (WT) controls. Histological analysis of the mutants showed accumulation of micro-vesicular cytoplasmic lipid droplets in the hepatocytes. However, gastric infusion of vitamin B and betaine complex significantly decreased the plasma levels of TG, TC and LDL-C in the CBS-KO rabbits, and alleviated hepatic steatosis compared to the untreated animals.
conclusionA CBS
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