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 APOE3 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 nucleotides of exon 2 such that expression is regulated by endogenous regulatory elements and the mouse APOE gene inactivated.

Other Phenotypes

Intermediate brain APOE and serum cholesterol levels compared with mice with knock-in of APOE4 or APOE2.

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 APOE3;R1.40 mice, APOE4;R1.40, and APOE2;R1.40 mice (Mann et al., 2004).

Phenotype Characterization

COMMENTS / QUESTIONS

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References

Research Models Citations

1. APP(Swedish) (R1.40)

Paper Citations

1. Mann KM, Thorngate FE, Katoh-Fukui Y, Hamanaka H, Williams DL, Fujita S, Lamb BT. 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