Key result
LDLR deletion in rats drives ~10-fold higher LDL-C and impairs hepatic lipid metabolism.
Answers are grounded in this paper and cite their sources.
The low-density lipoprotein receptor (LDLR) plays a critical role in the liver for the clearance of plasma low-density lipoprotein (LDL). Its deficiency causes hypercholesterolemia in many models. To facilitate the usage of rats as animal models for the discovery of cholesterol-lowering drugs, we took a genetic approach to delete the LDLR in rats aiming to increase plasma LDL cholesterol (LDL-C). An LDLR knockout rat was generated via zinc-finger nuclease technology, which harbors a 19-basepair deletion in the seventh exon of the ldlr gene. As expected, deletion of the LDLR elevated total cholesterol and total triglyceride in the plasma, and caused a tenfold increase of plasma LDL-C and a fourfold increase of plasma very low-density lipoprotein (VLDL-C). A lipidomics analysis revealed that deletion of the LDLR affected hepatic lipid metabolism, particularly lysophosphatidylcholines, free fatty acids and sphingolipids in the liver. Cholesterol ester (CE) 20:4 also displayed a significant increase in the LDLR knockout rats. Taken together, the LDLR knockout rat offers a new model of hypercholesterolemia, and the lipidomics analysis reveals hepatic lipid signatures associating with deficiency of the LDL receptor.
No takes yet. Share an insight, caveat, or question.
Wang et al. (2016) studied Hypercholesterolemia. LDLR gene deletion vs. Wild-type (implied) was evaluated on Plasma lipid levels and hepatic lipid metabolism. Deletion of the LDLR in a rat model caused hypercholesterolemia with a tenfold increase in plasma LDL-C, a fourfold increase in VLDL-C, and altered hepatic lipid metabolism.
Synapse has enriched 10 related papers. Consider them for comparative context: