Cited by 117Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthLipid metabolism and disorders

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Overexpression of Low Density Lipoprotein (LDL) Receptor Eliminates LDL from Plasma in Transgenic Mice

Hofmann, Sandra L., Russell, David W., Brown, Michael S., Goldstein, Joseph L., Hammer, Robert E.·1988·Science

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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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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)
ORCID: Hofmann, Sandra L.
Russell, David W.
Brown, Michael S.
Goldstein, Joseph L.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1988-03-11
Volume: 239
Issue: 4845
Pages: 1277-1281
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.3344433
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: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › 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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Overexpression of Low Density Lipoprotein (LDL) Receptor Eliminates LDL from Plasma in Transgenic Mice

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