Research Models

APOE3 Knock-In (Lamb)

Synonyms: APOE3 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 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

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Absent

No Data

  • Plaques
  • Tangles
  • Neuronal Loss
  • Gliosis
  • Synaptic Loss
  • Changes in LTP/LTD
  • Cognitive Impairment

Plaques

No data.

Tangles

No data.

Neuronal Loss

No data.

Gliosis

No data.

Synaptic Loss

No data.

Changes in LTP/LTD

No data.

Cognitive Impairment

No data.

Last Updated: 17 Jul 2018

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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.