Homozygous for a human APOE3 gene targeted replacement of the endogenous mouse Apoe gene
Expresses human apolipoprotein E3 isoform under the control of the murine Apoe regulatory sequences
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)
E3 is the most common isoform, expressed by almost 80% of the human population
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
On a high-fat diet, develops abnormal serum lipid profiles and atherosclerotic plaques
Exhibits an increased risk of atherosclerosis and hypercholesterolemia compared with wild type mice on a high fat diet, but not on a normal diet
Useful for studying the role of human APOE polymorphism in atherosclerosis, lipid metabolism and Alzheimer's disease
Genetic Background: C57BL/6 Background
The APOE3 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 APOE3 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. The colony is maintained through incrossing of homozygotes.
Carries Nnt mutation
Sullivan PM, Mezdour H, Aratani Y, Knouff C, Najib J, Reddick RL, Quarfordt SH, Maeda N. (1997) Targeted replacement of the mouse apolipoprotein E gene with the common human APOE3 allele enhances diet-induced hypercholesterolemia and atherosclerosis. J Biol Chem, 272(9):17972-80.