Research Models

TgAPPSwe-KI

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Species: Mouse
Genes: APP
Mutations: APP K670_M671delinsNL (Swedish)
Modification: APP: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: R1 line of ES cells
Availability: Unknown

Summary

This model was generated using a gene-targeting strategy designed to enhance the production of human Aβ in the mouse brain without changing APP synthesis. Site-specific mutations were introduced into exon 16 of the mouse APP gene to humanize the Aβ sequence and introduce the Swedish APP mutation (K670N/M671L). Because of this approach, these animals produce human Aβ in the absence of mouse Aβ. In addition, the APP gene retains the normal chromosomal position so developmental and tissue-specific expression pattens of Aβ are maintained. The lack of APP overexpression and the absence of mouse Aβ are key features of this model. The mice produce humanized Aβ, at elevated levels, leading to Aβ accumulation (Reaume et al., 1996).

The line of mice producing the highest amounts of human Aβ were designated APPNLh/APPNLh.

Modification Details

Modification of mouse APP sequence to introduce the  Swedish mutation and "humanize" the murine Aβ sequence by altering three amino acids. The mutant APP allele containing the neomycin-selectable marker in intron 15 (neo+) and the exon 16 mutations was designated as APPnNLh. Due to the uncertainty of the effect of the neo-selectable marker on APP expression in vivo, the PGK/neo gene was excised by recombination at the flanking loxP sites after transient expression of the Cre recombinase.

Last Updated: 25 Nov 2019

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References

Paper Citations

  1. Reaume AG, Howland DS, Trusko SP, Savage MJ, Lang DM, Greenberg BD, Siman R, Scott RW. Enhanced amyloidogenic processing of the beta-amyloid precursor protein in gene-targeted mice bearing the Swedish familial Alzheimer's disease mutations and a "humanized" Abeta sequence. J Biol Chem. 1996 Sep 20;271(38):23380-8. PubMed.

Further Reading

No Available Further Reading