Modification: APOE: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: B6.129P2-Apoetm1(APOE*2)Mae N9
Genetic Background: C57BL/6
Availability: Taconic: Stock# 1547-F and 1547-M
Targeted gene replacement was used to replace the endogenous murine APOE gene with the human APOE2 allele. In humans, the APOE2 allele is associated with decreased risk of Alzheimer's disease and an increased risk for type III hyperlipoproteinemia. Mice homozygous for the APOE2 allele exhibit characteristics of type III hyperlipoproteinemia. They have plasma cholesterol and triglyceride levels 2-3x higher than levels in mice expressing human APOE3. The APOE2 mice also have deficits in clearing very-low-density lipoprotein (VLDL) particles and spontaneously develop atherosclerotic plaques. A high fat diet exacerbates the atherosclerosis (Sullivan et al., 1998). The human APOE2 protein differs from the most common APOE isoform, APOE3, by a single amino acid at position 158.
Targeted gene replacement of the endogenous murine APOE gene with the human APOE2 allele. Targeting construct included exons 2-4 of APOE2.
- Sullivan PM, Mezdour H, Quarfordt SH, Maeda N. Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human Apoe*2. J Clin Invest. 1998 Jul 1;102(1):130-5. PubMed.
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