Research Models

App knock-in (humanized Aβ)

Synonyms: Apph, Apph/h

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Species: Rat
Genes: App
Modification: App: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: Long-Evans
Availability: Available through Luciano D'Adamio.

Summary

This knock-in model carries a humanized Aβ sequence within the endogenous rat App gene (Tambini et al., 2019).

Levels of App mRNA in brain were similar in 21-day-old rats homozygous for the humanized App gene (Apph/h) and wild-type animals (Appw/w).

This line has been used as a control to study the effects of the AD-linked Swedish mutation and the protective Icelandic mutation in rat models.

Modification Details

CRISPR/Cas9 was used to edit the endogenous rat App gene, generating a humanized Aβ sequence through the following mutations (amino acid positions numbered as in Aβ1-40): G5R (GGA > CGA), F10Y (TTC > TAC), and R13H (CGC > CAT).

App-mutation carriers were crossed five times to wild-type Long-Evans rats to reduce the probability of off-target mutations, then male and female rats heterozygous for the humanized sequence (F5-Apph/w) were bred to generate rats homozygous for humanized Aβ.

Related Strains

Apps knock‐in. This knock-in rat model carries the Swedish double mutation and a humanized Aβ sequence within the endogenous rat App gene.

Appp knock‐in. This knock-in rat model carries the Icelandic mutation and a humanized Aβ sequence within the endogenous rat App gene.

 

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

  • Plaques
  • Tangles
  • Neuronal Loss

No Data

  • Gliosis
  • Synaptic Loss
  • Changes in LTP/LTD
  • Cognitive Impairment

Plaques

None observed at 3 months.

Tangles

None observed at 3 months.

Neuronal Loss

None observed at 3 months.

Gliosis

No data.

Synaptic Loss

No data.

Changes in LTP/LTD

No data.

Cognitive Impairment

No data.

Last Updated: 08 Apr 2020

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References

Mutations Citations

  1. APP K670_M671delinsNL (Swedish)
  2. APP A673T (Icelandic)

Research Models Citations

  1. App knock‐in (Swedish mutation and humanized Aβ)
  2. App knock‐in (Icelandic mutation and humanized Aβ)

Paper Citations

  1. Tambini MD, Yao W, D'Adamio L. Facilitation of glutamate, but not GABA, release in Familial Alzheimer's APP mutant Knock-in rats with increased β-cleavage of APP. Aging Cell. 2019 Dec;18(6):e13033. Epub 2019 Sep 9 PubMed.

Other Citations

  1. Luciano D'Adamio

Further Reading

No Available Further Reading