The DOI matches its Crossref record.
Human Apolipoprotein E2, E3, and E4 Isoform-Specific Transgenic Mice: Human-like Pattern of GlialandNeuronal Immunoreactivity in Central Nervous System Not Observed in Wild-Type Mice
Abstract
Apolipoprotein E (apoE) and its three major alleles (APOE2, E3, and E4) have been implicated in Alzheimer's disease and other neurological disorders. Little is known of the role apoE plays in normal brain function and pathology. To create a model to study apoE in brain, we have generated APOE transgenic mice using microinjection of allele-specific human genomic fragments to establish founders which were then bred to APOE knockout mice lacking a functional mouse apoE protein. This allows the study of apoE without interference from the endogenous mouse APOE gene. Results demonstrate that transgenic lines have been established that transcribe and express apoE appropriately in brain, liver, and other tissues. High cholesterol levels found in APOE knockout mice are substantially corrected in the APOE transgenic lines. ApoE immunoreactivity has been detected in glial cells and selected classes of neurons in all three isoform-specific transgenics. This pattern of immunoreactivity is similar to that observed in nonhuman primates and man, and contrasts with the strictly glial staining pattern of normal rodents.
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In the citing paper
“These mice express ApoE via the endogenous promoter, and as a result, the turnover of ApoE should reflect the natural synthesis and clearance rates of the protein [22].”
From In Vivo Human Apolipoprotein E Isoform Fractional Turnover Rates in the CNS (2012) · cites this paper as [22]
In the citing paper
“However, under aging and stress conditions, neurons also produce apoE, albeit at lower levels than astrocytes [25, 26].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [26]
In the citing paper
“working model: Aging and/or stress induces neuronal expression of apoE.”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [26]
Citations
Cited by
Sorted by citations
The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661
“Following these initial studies with apoE knock-out mice, several lines of transgenic mice were generated to study the role of human apoE isoforms in AD pathogenesis (Raber et al., 1998; Sun et al., 1998; Xu et al., 1996).”
Mahley, R. W., Weisgraber, K. H., & Huang, Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600549103 · Cited by 912
Pharmacogenetics and the practice of medicine
Roses, A. D. (2000) · Nature · doi:10.1038/35015728 · Cited by 806
Self-citationSullivan, P. M., Mezdour, H., Aratani, Y., Knouff, C., Najib, J., Reddick, R. L., Quarfordt, S. H., & Maeda, N. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.29.17972 · Cited by 575
Self-citationXu, Q., Bernardo, A., Walker, D., Kanegawa, T., Mahley, R. W., & Huang, Y. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.5476-05.2006 · Cited by 524
“…that at least some neurons express apoE (Diedrich et al., 1991; Poirier et al., 1991; Han et al., 1994; Bao et al., 1996; Metzger et al., 1996; Xu et al., 1996, 1999a,b; Dupont-Wallois et al., 1997; Boschert et al., 1999; Ferreira et al., 2000; Dekroon and Armati, 2001; Hartman et al., 2001;…”
Background
Metadata
- Authors
- Xu, P.-T., Schmechel, D., Rothrock-Christian, T., Burkhart, D. S., Qiu, H.-L., Popko, B., Sullivan, P., Maeda, N., Saunders, A. M., Roses, A. D., & Gilbert, J. R.
- Affiliations
- Duke University (US)
- University of North Carolina at Chapel Hill (US)
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 1996-06
- Volume
- 3
- Issue
- 3
- Pages
- 229-245
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2081122171
- Cited by
- 178
- References
- 0
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 2 · 2014: 2 · 2013: 4 · 2012: 6
- FWCI
- 7.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r35ag007922-07)
- National Institute on Aging (AG05 128, P50AG005128, AG07922)
- National Institute of Environmental Health Sciences (Y01-ES-40290)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- apolipoprotein E, APOE isoforms, APOE2, APOE3, APOE ε4, transgenic mice, ApoE-deficient mice, glial cells, neuronal expression, central nervous system, Alzheimer's disease, cholesterol levels
- MeSH terms
- Alleles, Animals, Apolipoproteins E, Central Nervous System, DNA, Humans, Mice, Transgenic, Neuroglia, Neurons, Reference Values, Transcription, Genetic, Protein Biosynthesis, Gene Library, Genome, Transgenes, Mice, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2
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