Apolipoprotein E knock-out and knock-in mice: atherosclerosis, metabolic syndrome, and beyond
Open accessAbstract
Given the multiple differences between mice and men, it was once thought that mice could not be used to model atherosclerosis, principally a human disease. Apolipoprotein E-deficient (apoEKO) mice have convincingly changed this view, and the ability to model human-like plaques in these mice has provided scientists a platform to study multiple facets of atherogenesis and to explore potential therapeutic interventions. In addition to its well-established role in lipoprotein metabolism, recent observations of reduced adiposity and improved glucose homeostasis in apoEKO mice suggest that apoE may also play a key role in energy metabolism in peripheral organs, including adipose tissue. Finally, along with apoEKO mice, knockin mice expressing human apoE isoforms in place of endogenous mouse apoE have provided insights into how quantitative and qualitative genetic alterations interact with the environment in the pathogenesis of complex human diseases.
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ApoE deficiency disrupts lipid homeostasis, resulting in elevated cholesterol and triglyceride levels in plasma from early adulthood.
“Conversely, ApoE deficiency disrupts lipid homeostasis, resulting in elevated cholesterol and triglyceride levels in plasma from early adulthood.”
From Dyslipidemia-Induced Mitochondrial Dysfunctions in the Brains Does Not Reach Pathological Levels in the ApoE-Knockout Mice (2026) · cites this paper as [31]
The “LIPOPROTEIN METABOLISM IN APOEKO MICE” section reports elevated plasma cholesterol and accumulation of cholesterol-rich remnants in apoE-deficient mice. The figure caption in “APOE IN DIABETES AND BEYOND” also describes impaired triglyceride uptake, but the copy does not establish elevated plasma triglyceride levels or specify that these changes begin in early adulthood. The claim is therefore supported for disrupted lipid metabolism and elevated cholesterol, but not for those added details. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMice homozygous for ApoE loss-of-function alleles develop atherosclerosis and have been used as a model of cardiovascular disease due to lipid dysregulation.
“Mice homozygous for ApoE loss-of-function alleles develop atherosclerosis and have been used as a model of cardiovascular disease due to lipid dysregulation [31].”
From Dyslipidemia-Induced Mitochondrial Dysfunctions in the Brains Does Not Reach Pathological Levels in the ApoE-Knockout Mice (2026) · cites this paper as [31]
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“In contrast, mice with human apoE2, which binds to LDLR with less affinity, accumulate plasma remnants with high cholesterol and triglycerides (TG) and develop atherosclerosis (16).”
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Apolipoprotein E isoforms and lipoprotein metabolism
Phillips, M. C. (2014) · IUBMB Life · doi:10.1002/iub.1314 · Cited by 328 · see citing works
Sacks, F. M. (2015) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000146 · Cited by 168 · see citing works
Lipolysis of triglyceride-rich lipoproteins, vascular inflammation, and atherosclerosis
Schwartz, E. A., & Reaven, P. D. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.09.021 · Cited by 130 · see citing works
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Antiatherosclerotic Effect of an Antibody That Binds to Extracellular Matrix Glycosaminoglycans
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Hsu, C.-H., Chu, P.-W., Chen, Y.-Y., Ho, M.-H., Liao, E.-C., & Chen, S.-K. (2026) · Neurochemical Research · doi:10.1007/s11064-026-04842-3
- Authors
- Pendse, A. A., Arbones-Mainar, J. M., Johnson, L. A., Altenburg, M. K., & Maeda, N.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 50
- Pages
- S178-S182
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC2674752
- OpenAlex
- W2052435494
- Cited by
- 155
- References
- 5
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 9 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 12 · 2019: 7 · 2018: 14 · 2017: 8 · 2016: 16 · 2015: 15 · 2014: 6 · 2013: 8 · 2012: 13
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL042630, R37HL042630, R01HL077145, R01HL042630)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- apolipoprotein E, ApoE-deficient mice, atherosclerosis, atherogenesis, metabolic syndrome, lipoprotein metabolism, energy metabolism, adipose tissue, glucose homeostasis, adiposity, genetic disease modeling
- MeSH terms
- Animals, Apolipoproteins E, Diabetes Mellitus, Humans, Mice, Transgenic, Adipocytes, Protein Isoforms, Metabolic Syndrome, Atherosclerosis, Mice
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