Research Models

TetO-APPSweInd (line 102)

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Species: Mouse
Genes: APP
Mutations: APP KM670/671NL (Swedish), APP V717F (Indiana)
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: B6.Cg-Tg(tetO-APPSwInd)102Dbo/Mmjax
Genetic Background: C57BL/6 x C3HeJ; backcrossed to C57BL/6
Availability: The Jackson Lab; available through the JAX MMRRC Stock# 034845; Cryopreserved

Summary

These mice enable regulated expression of mutant APP using a tet-off system. A tetracycline-responsive promoter drives expression of the APP transgene which carries the Swedish and Indiana mutations. When bred to transgenic mice expressing reverse tertracyclin-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA) the expression of the transgene can be turned off with the tetracycline analog, doxycycline, in bigenic animals.

Four lines of bigenic animals were reported simultaneously (Jankowsky et al., 2005). All four lines express APP protein at levels 10-30 fold higher than endogenous mouse APP and the transgene is nearly completely suppressed (>95 percent) following doxycycline treatment for as little as two weeks. Of the four lines, line 102 had the greatest sensitivity to doxycycline (see also line 107 and line 885).

When bred to animals producing tTA under the control of the CAMKIIα promoter, bigenic mice overproduce Aβ42 and amyloid deposition occurs as early as two months of age. Amyloid burden increases with age and by nine months the hippocampus and cortex have extensive amyloid pathology. Suppression of the APP transgene with doxycycline halts the progression of amyloid pathology. Mice also have progressive neuronal atrophy especially in the granule cell layer of the dentate gyrus (Jankowsky et al., 2005).

This model was previously available through The Jackson Lab as Stock# 007051.

Modification Details

Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2.

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References

Research Models Citations

  1. TetO-APPSweInd (line 107)
  2. TetO-APPSweInd (line 885)

Paper Citations

  1. . Persistent amyloidosis following suppression of Abeta production in a transgenic model of Alzheimer disease. PLoS Med. 2005 Dec;2(12):e355. Epub 2005 Nov 15 PubMed.

External Citations

  1. JAX MMRRC Stock# 034845

Further Reading