Research Models

APOE2 Knock-In, floxed (CureAlz)

Synonyms: E2F

Species: Mouse
Genes: APOE
Modification: APOE: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: C57BL/6J
Availability: Available through a material transfer agreement with the Cure Alzheimer’s Fund.

Summary

This knock-in mouse belongs to a set of models designed to allow investigators to compare the effects of the various human APOE isoforms and to conditionally disrupt APOE expression. In this version, “E2F,” the coding region of the mouse Apoe gene was replaced with the human APOE2 sequence flanked by loxP sites. (“E3F” and “E4F,” the others in the series, respectively carry the APOE ε3 and ε4 alleles.) The mice express full-length human ApoE protein under the control of endogenous mouse regulatory elements. When crossed with mice carrying Cre transgenes under the control of inducible or cell-type-specific promoters, researchers can test the effects of disrupting APOE expression at particular times or in selected cell types. When crossed with mouse models of amyloidosis or tauopathy, this series of knock-in mice also can be used to compare the effects of the various human ApoE isoforms on Alzheimer’s-related pathology.

ApoE protein is found in astrocytes in the brains of these mice, but is absent from Iba1-positive microglia.

The APOE knock-in mice have been crossed with APP/PS1 mice, a model of amyloidosis. In 4-month-old mice homozygous for the human APOE ε2 allele, ApoE immunoreactivity was observed in the center of plaques and in microglia, as well as in astrocytes. Cortical plaque burdens (percent area occupied by plaques), plaque size, and plaque density were similar in male and female E2F mice, when plaques were visualized using either an antibody directed against Aβ or the X-34 stain that binds to fibrillar Aβ. Plaque burdens and plaque sizes in E2F mice did not differ from E3F or E4F mice, although the density of X-34-positive plaques was lower in E2F females than in E4F females.

The influence of peripherally derived ApoE on amyloid accumulation has been tested in these mice. E2F mice were first crossed with mice carrying a Cre transgene under the control of the albumin promoter, in order to ablate APOE in hepatocytes, the major source of circulating ApoE. Mice with this targeted deletion of APOE were then crossed with APP/PS1 mice. As expected, levels of circulating ApoE were greatly reduced in the progeny from these crosses, and there were some changes in plasma lipid profiles, but the reduction in peripherally-derived ApoE did not affect cerebral amyloid accumulation.

Modification Details

The coding region of the mouse Apoe gene, from the translation initiation codon in exon 2 to the termination codon in exon 4, was replaced with the corresponding human APOE (ε2 allele) sequence, flanked by loxP sites.

Related Strains

APOE3 Knock-In, floxed (CureAlz). This knock-in mouse belongs to the set of models with a humanized APOE gene “floxed” to allow conditional disruption of APOE expression. In this case, the coding region of the mouse Apoe gene was replaced with the human APOE3 sequence flanked by loxP sites.

APOE4 Knock-In, floxed (CureAlz). This knock-in mouse belongs to the set of models with a humanized APOE gene “floxed” to allow conditional disruption of APOE expression. In this case, the coding region of the mouse Apoe gene was replaced with the human APOE4 sequence flanked by loxP sites.

 

 

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: 08 Nov 2019

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References

Research Models Citations

  1. APPPS1
  2. APOE3 Knock-In, floxed (CureAlz)
  3. APOE4 Knock-In, floxed (CureAlz)

External Citations

  1. Cure Alzheimer’s Fund

Further Reading

No Available Further Reading