- Homozygous for a human APOE2 gene targeted replacement of the endogenous mouse Apoe gene
- Expresses human apolipoprotein E2 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)
- E2 is the least common isoform in the human population
- In humans, the E2 allele decreases the risk and delays onset of AD, but increases the risk of type III hyperlipoproteinemia
- Develops hyperlipoproteinemia with elevated plasma cholesterol and triglyceride levels, decreased clearance of vLDL particles, and spontaneous atherosclerotic plaques on a normal diet, exacerbated by a high fat diet
- Useful for studying the role of human APOE polymorphism in atherosclerosis, lipid metabolism and Alzheimer's disease
Genetic Background: C57BL/6 Background
The APOE2 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 APOE2 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 two additional times (N9) and embryo transfer derived. The colony is maintained through incrossing of homozygotes.
Wild type for Nnt mutation
Sullivan PM, Mezdour H, Quarfordt SH, Maeda N. (1998) Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse apoe with human APOE*2. J Clin Invest, 102(1):130-5.