Overexpression of low density lipoprotein (LDL) receptor eliminates LDL from plasma in transgenic mice
Abstract
A complementary DNA encoding the human low density lipoprotein (LDL) receptor under control of the mouse metallothionein-I promoter was injected into fertilized mouse eggs, and a strain of mice expressing high levels of LDL receptors was established. After administration of cadmium, these mice cleared intravenously injected 125I-labeled LDL from blood eight to ten times more rapidly than did normal mice. The plasma concentrations of apoproteins B-100 and E, the two ligands for the LDL receptor, declined by more than 90 percent after cadmium treatment, but the concentration of another apoprotein, A-I, was unaffected. Therefore, overexpression of an endocytotic receptor can dramatically lower the ambient concentration of its ligand in vivo.
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Overexpression of LDLR in the liver facilitated LDL elimination by receptor-mediated endocytosis and prevented diet-induced hypercholesterolemia.
“Overexpression of LDLR in the liver facilitated LDL elimination by receptor-mediated endocytosis and prevented diet-induced hypercholesterolemia (Hofmann et al., 1988; Yokode et al., 1990).”
From Overexpression of Low-Density Lipoprotein Receptor in the Brain Markedly Inhibits Amyloid Deposition and Increases Extracellular Aβ Clearance (2009) · cites this paper as Hofmann et al., 1988
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- Authors
- Hofmann, S. L., Russell, D. W., Brown, M. S., Goldstein, J. L., & Hammer, R. E.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Venue
- Science
- Published
- 1988-03-11
- Volume
- 239
- Issue
- 4845
- Pages
- 1277-1281
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2081393029
- Cited by
- 117
- References
- 28
- Citations by year
- 2023: 2 · 2022: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2013: 1 · 2012: 1
- FWCI
- 15.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-20948, HL 01287)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- LDL receptor, transgenic mice, metallothionein-I promoter, cadmium, LDL clearance, apolipoprotein B-100, apolipoprotein E, apolipoprotein A-I, endocytic receptor, ligand concentration, lipoprotein metabolism
- MeSH terms
- Animals, Cloning, Molecular, DNA, Female, Genes, Humans, Kinetics, Lipoproteins, LDL, Mice, Transgenic, Plasmids, Receptors, LDL, Reference Values, Transcription, Genetic, Mice
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