General Information

Transgene: APOE KI mice (see Hamanaka, 2000) were backcrossed onto a C57BL/6J (B6) inbred background and mated to ZP3-cre tg mice to remove the neo cassette through cre-mediated loxP excision, and the resulting offspring inherited the targeted allele lacking the neo tag.

Mutation: Replaced mouse Apoe with human APOE2

Promoter: Mouse Apoe

Mouse Strain: 129P2/OlaHsd (ES cell line E14TG2aIV). Backcrossed, N8.

Phenotype

Neuropathological Analysis:

APOE abundance in the brains of APOE2 KI animals as well as high serum cholesterol levels when compared to APOE3 and APOE4 KI animals. APOE2 KI mice crossed with APP B6-R1.40 mice and the bigenic mice had slightly higher levels of brain cholesterol relative to non-tg animals. The presence of human APOE significantly increases brain Aβ levels in a genomic-based model of AD, irrespective of genotype.

Availability

Bruce Lamb
Department of Genetics
Case Western Reserve University
10900 Euclid Avenue
Cleveland, OH 44106-4955, USA
Phone: (216)368-2979
Fax: (216)368-3432
Email: btl@cwru.edu

Patents:

References

Primary:

Mann KM, Thorngate FE, Katoh-Fukui Y, Hamanaka H, Williams DL, Fujita S, Lamb BT. Independent effects of APOE on cholesterol metabolism and brain A{beta} levels in an Alzheimer disease mouse model. Hum Mol Genet. 13: 1959-1968, 2004. Abstract

Associated:

Hamanaka H, Katoh-Fukui Y, Suzuki K, Kobayashi M, Suzuki R, Motegi Y, Nakahara Y, Takeshita A, Kawai M, Ishiguro K, Yokoyama M, and Fujita SC. Altered cholesterol metabolism in human apolipoprotein E4 knock-in mice. Hum. Mol. Genet. 9: 353-361, 2000. Abstract