Research Models

APOE2 Knock-In

Synonyms: APOE2 KI

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Species: Mouse
Genes: APOE
Modification: APOE: Knock-In
Disease Relevance: Alzheimer's Disease, Traumatic Brain Injury
Strain Name: N/A
Genetic Background: C57BL/6; 129P2, backcrossed to C57BL/6J
Availability: No longer available through Bruce Lamb

Modification Details

The human APOE2 cDNA sequence was knocked-in at the endogenous mouse APOE locus; inserted in frame with non-coding sequences, exon 1, intron 1 and the first 18 bp of exon 2 such that expression is regulated by endogenous regulatory elements and the mouse APOE gene inactivated.

Other Phenotypes

On average, these mice had 2-fold higher level of steady state APOE in the brain and significantly higher APOE in serum compared with APOE3 knock-in and APOE4 knock-in animals. They also had the highest levels of serum cholesterol and triglycerides after a six hour fast.

Note

When crossed with R1.40 mice, a YAC-based model that overexpresses APP with the Swedish mutation, no changes in holo-APP or APP C-terminal fragments were observed. The double-cross mice did have significantly higher levels of Aβ40 compared with R1.40 mice with endogenous APOE. No significant differences in Aβ40 levels between APOE2;R1.40 mice, APOE4;R1.40, and APOE3;R1.40 mice (Mann et al., 2004).

Last Updated: 16 Oct 2013

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References

Research Models Citations

  1. APP(Swedish) (R1.40)

Paper Citations

  1. . Independent effects of APOE on cholesterol metabolism and brain Abeta levels in an Alzheimer disease mouse model. Hum Mol Genet. 2004 Sep 1;13(17):1959-68. PubMed.

Further Reading

Papers

  1. . Altered cholesterol metabolism in human apolipoprotein E4 knock-in mice. Hum Mol Genet. 2000 Feb 12;9(3):353-61. PubMed.