Cited by 2,263Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthAtherosclerosis and Cardiovascular Diseases

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Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells

Plump, Andrew S., Smith, Jonathan D., Hayek, Tony, Aalto-Setälä, Katriina, Walsh, Annemarie, Verstuyft, Judy G., Rubin, Edward M., Breslow, Jan L.·1992·Cell

DOI 10.1016/0092-8674(92)90362-g

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Abstract

apoE-deficient mice have been created by homologous recombination in ES cells. On a low fat, low cholesterol chow diet these animals have plasma cholesterol levels of 494 mg/dl compared with 60 mg/dl in control animals, and when challenged with a high fat Western-type diet, these animals have plasma cholesterol levels of 1821 mg/dl compared with 132 mg/dl in controls. This marked hypercholesterolemia is primarily due to elevated levels of very low and intermediate density lipoproteins. At 10 weeks of age, apoE-deficient mice have already developed atherosclerotic lesions in the aorta and coronary and pulmonary arteries. apoE-deficient mice are a promising small animal model to help understand the role of apoE in vivo and the genetic and environmental determinants of atherosclerosis.

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Self-citation

Authors: Plump, A. S., Smith, J. D., Hayek, T., Aalto-Setälä, K., Walsh, A., Verstuyft, J. G., Rubin, E. M., & Breslow, J. L.
Affiliations: Rockefeller University (US)
Lawrence Berkeley National Laboratory (US)
ORCID: Smith, Jonathan D.
Rubin, Edward M.
Breslow, Jan L.
Venue: Cell
Publisher: Elsevier BV
Published: 1992-10
Volume: 71
Issue: 2
Pages: 343-353
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/0092-8674(92)90362-g
OpenAlex: W2048890665
Cited by: 2,263
References: 45
Citations by year: 2026: 23 · 2025: 41 · 2024: 28 · 2023: 32 · 2022: 52 · 2021: 39 · 2020: 60 · 2019: 69 · 2018: 57 · 2017: 66 · 2016: 57 · 2015: 71 · 2014: 71 · 2013: 82 · 2012: 75
FWCI: 72.03
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01hl033714-17)
National Heart, Lung, and Blood Institute (HL 33714, R01HL032435, HL32435)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords: apolipoprotein E deficiency, hypercholesterolemia, atherosclerosis, ApoE-deficient mice, homologous recombination, embryonic stem cells, serum cholesterol, VLDL, intermediate density lipoprotein, high-fat diet, aortic atherosclerotic lesions, coronary arteries, pulmonary artery, animal models of atherosclerosis
MeSH terms: Animals, Aorta, Apolipoproteins E, Arteriosclerosis, Cholesterol, Coronary Vessels, Disease Models, Animal, Hypercholesterolemia, Lipoproteins, Lipoproteins, VLDL, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Pulmonary Artery, Stem Cells, Mice, Lipoproteins, IDL

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Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells

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