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Homozygous for a human APOE4 gene targeted replacement of the endogenous mouse Apoe gene
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Expresses human apolipoprotein E4 isoform under the control of the murine Apoe regulatory sequences
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ApoE is a plasma protein involved in cholesterol transport, with three human isoforms (E2, E3, and E4) that have been associated with atherosclerosis and Alzheimer's Disease (AD)
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E4 occurs in approximately 14% of the human population
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In humans, the E4 allele is associated with increased plasma cholesterol and a greater risk of coronary artery disease
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On a normal diet, this model has normal plasma cholesterol and triglyceride levels, but altered relative quantities of different plasma lipoprotein particles, and delayed clearance of vLDL particles, with only half the clearance rate observed in the APOE3 targeted replacement mice
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On a high-fat diet, develops abnormal serum lipid profiles and atherosclerotic plaques that are more severe than the APOE3 model, with twice the cholesterol, ApoE, and ApoB-48 levels and larger plaques than the APOE3 model
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Exhibits an increased risk of atherosclerosis compared with wild type and APOE3 targeted replacement mice
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Useful for studying the role of human APOE polymorphism in atherosclerosis, lipid metabolism and Alzheimer's disease
Orders by weight: Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation.
Genetic Background:
C57BL/6NTac background, nearly congenic on C57BL/6NTac background with non-C57BL/6NTac character remaining in a few loci. Origin:
The APOE4 targeted replacement mouse was developed in the laboratory of Nobuya Maeda at the University of North Carolina. The model was created by targeting the murine Apoe gene for replacement with the human APOE4 allele in E14TG2a ES cells and injecting the targeted cells into blastocysts. Resultant chimeras were backcrossed to C57BL/6 for seven generations (N7). Taconic received stock in 2000. The mice were backcrossed once more (N8) and embryo transfer derived. Additional backcrossing to C57BL/6NTac was completed and the line is nearly congenic on C57BL/6NTac, with a few loci remaining which are not consistent with C57BL/6NTac. The colony is maintained through mating of homozygotes.
Genetics:
Does not carry Nnt mutation
Color:
Black Species:
Mouse Initial Publication:
Knouff C, Hinsdale ME, Mezdour H, Altenburg MK, Watanabe M, Quarfordt SH, Sullivan PM, Maeda N. (1999) ApoE structure determines VLDL clearance and atherosclerosis risk in mice. J Clin Invest, 103(11):1579-86.
