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.
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 APOE4;R1.40 mice, APOE2;R1.40 and APOE4;R1.40 mice (Mann et al., 2004).
The human APOE4 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.
Research Models Citations
- 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.
No Available Further Reading