Modification: APOE: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: B6(SJL)-ApoEtm1.1(APOE*4)Adiuj/J
Genetic Background: C57BL/6J
Availability: The Jackson Laboratory, Stock # 027894; Live
APOE4 knock-in mice express a humanized APOE4 allele from the endogenous ApoE locus. APOE was humanized by replacing mouse ApoE exons 2, 3, and most of exon 4, with human APOE4 sequence including exons 2, 3, 4 and a portion of the 3' UTR sequence.
Homozygotes are viable and fertile.
The data summarized here were reported at the 2018 AAIC meeting. At 2 and 12 months of age, locomotor activity (distance traveled in an open field test) and motor coordination (latency to fall on rotarod test) are similar in APOE4 KI and C57BL/6J control mice, with both genotypes showing an age-dependent decline in these measures. Two- and 12-month-old APOE4 mice also performed similarly to control mice in a Y-maze test of working memory.
While control mice gained weight, at least until 14 months of age, the body weights of APOE4 KI mice were stable between 4 and 14 months.
At 4 and 14 months, levels of total cholesterol and LDL were decreased in the sera of male and female APOE4 KI mice, compared with controls. A reduction in the levels of HDL was seen in males at 4 months and in both genders at 14 months. Levels of triglycerides and non-essential fatty acids were normal.
The ApoE gene in C57BL/6J mouse embryonic stem cells was humanized through homologous recombination using a targeting vector containing 1.5 kb of human APOE gene sequence (the APOE4 isoform) including exons 2, 3, 4, and a portion of the 3' UTR sequence (this vector also contained a FRT-flanked Neo cassette to select for stem cells that had successfully integrated the vector). Mice were generated by injection of the genetically modified stem cells into donor embryos. Chimeric animals were bred to C57BL/6J mice, and progeny were crossed to FLP recombinase-expressing mice to remove the Neo cassette. The resulting Neo-negative mice were then backcrossed to C57BL/6J animals to remove the FLP recombinase transgene.
APOE3 Knock-In (JAX). APOE3 knock-in mice express humanized APOE3 from the endogenous ApoE locus.
Trem2 R47H KI x APOE4. This double-mutant line (The Jackson Lab:Stock# 028709) was generated by crossing the line carrying a humanized APOE4 gene (Jackson Lab Stock #027894) to a line carrying an R47H point mutation knocked into the mouse Trem2 gene (Jackson Lab Stock #027918).
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
- Cognitive Impairment
- Neuronal Loss
- Synaptic Loss
- Changes in LTP/LTD
Changes in LTP/LTD
At 2 and 12 months of age, APOE4 KI mice perform similarly to wild-type mice in tests of locomotor activity, motor coordination, and working memory.
Last Updated: 30 Nov 2018
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