Species: Mouse
Genes: APP
Mutations: APP K670_M671delinsNL (Swedish), APP T714I (Austrian)
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: C57BL/6J
Availability: Unknown

Summary

This APP transgenic overexpresses mutant human APP under the control of the Thy-1.2 promoter, driving neuronal expression. The transgene carries two mutations associated with familial Alzheimer’s disease: the Swedish double mutation (K670N/M671L) and the Austrian mutation (T714I). The expression level of human APP was reported as approximately 1.4-fold endogenous APP (Yamada et al., 2009).

These mice develop progressive amyloid deposition in the cerebral cortex at approximately at 9-12 months of age. By 21 months amyloid pathology is extensive.

The A7 line was used to investigate the effects of chronic optogenetic stimulation on Aβ production and amyloid plaque development. Neuronal hyperexcitability in the hippocampus increased interstitial Aβ42 and plaque burden in the projection area of the perforant pathway. Light stimulation in the optogenetically altered animals also elicited seizures. Seizures were not observed in the absence of optogenetic stimulation (Yamamoto et al., 2015).

Modification Details

The transgene expressed by these mice encodes mutant APP with the Swedish mutation (K670N/M671L) and the Austrian mutation (T714I) under the control of the Thy1.2 promoter.

Phenotype Characterization

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References

Paper Citations

1. Yamada K, Yabuki C, Seubert P, Schenk D, Hori Y, Ohtsuki S, Terasaki T, Hashimoto T, Iwatsubo T. Abeta immunotherapy: intracerebral sequestration of Abeta by an anti-Abeta monoclonal antibody 266 with high affinity to soluble Abeta. J Neurosci. 2009 Sep 9;29(36):11393-8. PubMed.
2. Yamamoto K, Tanei Z, Hashimoto T, Wakabayashi T, Okuno H, Naka Y, Yizhar O, Fenno LE, Fukayama M, Bito H, Cirrito JR, Holtzman DM, Deisseroth K, Iwatsubo T. Chronic optogenetic activation augments aβ pathology in a mouse model of Alzheimer disease. Cell Rep. 2015 May 12;11(6):859-65. Epub 2015 Apr 30 PubMed.

Further Reading