Research Models

App knock-in (humanized Aβ)

Synonyms: Apphu/hu

Species: Mouse
Genes: App
Modification: App: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: Appem1Bdes
Genetic Background: C57BL6J
Availability: Available through Lutgarde Serneels.

Summary

Apphu/hu mice carry a humanized Aβ sequence within the murine App gene. In this knock-in model, created using CRISPR/Cas9 technology, expression of App is driven by its natural promoter and is expected to show normal cell-type and temporal specificity. Levels of APP are similar in the brains of Apphu/hu and wild-type mice, but the knock-in mice contain more CTFβ, consistent with more efficient BACE1 processing of human APP than rodent APP.

Levels of APP and its metabolites have been measured in the brains of 14-week-old mice. As mentioned, the amount of full-length APP did not differ between Apphu/hu and wild-type mice. However, brains of the knock-in animals contained approximately 2.5 times more CTFβ and about two-thirds less CTFα than wild-type controls. Levels of Aβ40 more than doubled in the knock-ins compared with wild-type. Aβ38 and Aβ42 were not detectable in wild-type animals but were present at measurable levels in the knock-in animals, as was Aβ43.

Levels of tau (total, 3R, or 4R isoforms) did not differ between Apphu/hu and wild-type mice.

These mice, which generate wild-type human Aβ, should be particularly useful as controls in experiments studying the effects of AD-linked mutations in App knock-in mice.

Modification Details

CRISPR/Cas9 was used to introduce the following mutations into the endogenous App gene: G676R (G5R), F681Y (F10Y), R684H (R13H), numbered according to the 770 amino-acid isoform of human APP (position within the Aβ sequence).

 

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: 22 Oct 2020

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References

External Citations

  1. Lutgarde Serneels

Further Reading

No Available Further Reading