Research Models

App knock-in (humanized Aβ)

Synonyms: Apph, Apph/h

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 KM670/671NL
  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. . 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