Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells
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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The increased amounts of apoA-IV in VLDL and IDL observed in the patient were also seen in other reports of apoE deficiency and in apoE-deficient mice.
“The increased amounts of apoA-IV in VLDL and IDL we observed were seen in other reports of apoE deficiency4,5,9 and in apoE-deficient mice.31”
From Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function (2014) · cites this paper as [31]
Increased amounts of apoA-I were observed in LDL from an apoE-deficient patient and in VLDL from ApoE knockout mice.
“Increased amounts of apoA-I were observed in LDL from an apoE-deficient patient9 and in VLDL from ApoE knockout mice.31”
From Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function (2014) · cites this paper as [31]
ApoE-deficient mice are used as model animals for atherosclerosis.
“Disorders of apoE are associated with atherosclerosis, which causes dyslipidemia and myocardial infarction, and apoE-deficient mice are used as model animals for atherosclerosis2, 3).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [3]
Disorders of apoE are associated with atherosclerosis, which causes dyslipidemia and myocardial infarction.
“Disorders of apoE are associated with atherosclerosis, which causes dyslipidemia and myocardial infarction, and apoE-deficient mice are used as model animals for atherosclerosis2, 3).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [3]
Mutations in apoE that diminish binding of apoE-containing lipoproteins to the LDL receptor are associated with high plasma cholesterol levels and cause premature atherosclerosis in humans and experimental animals.
“In vivo and in vitro studies have shown that mutations in apoE that diminish binding of apoE-containing lipoproteins to the LDL receptor are associated with high plasma cholesterol levels and cause premature atherosclerosis in humans and experimental animals ( 1-3, 7, 8 ).”
From Molecular etiology of a dominant form of type III hyperlipoproteinemia caused by R142C substitution in apoE4 (2011) · cites this paper as [1]
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- 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)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1992-10
- Volume
- 71
- Issue
- 2
- Pages
- 343-353
- ISSN
- 0092-8674 (ISSN-L)
- 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
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl033714-17)
- National Heart, Lung, and Blood Institute (HL 33714, R01HL032435, HL32435)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › 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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