Research Models

APPSwe/PSEN1(A246E)

Synonyms: APPSwe (line C3-3)/PSEN1(A246E), APP/PS1

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Species: Mouse
Genes: APP, PSEN1
Mutations: APP KM670/671NL (Swedish), PSEN1 A246E
Modification: APP: Transgenic; PSEN1: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J
Genetic Background: Origin: (C57BL/6J x C3H/HeJ)F2
Availability: The Jackson Lab: Stock# 003378; Cryopreserved

Summary

These double transgenic mice were created by breeding mice which express the human PSEN1 gene carrying the A246E mutation with mice expressing a chimeric APP protein with the Swedish mutation (see APPSwe line C3-3). These mice exhibit elevated Aβ42(43) peptide in the brain, and by nine months develop numerous amyloid deposits which increase dramatically in number between ten and twelve months of age (Borchelt et al., 1997). Aβ42 and Aβ40 codeposit (Jankowsky et al., 2004).

Modification Details

These are double transgenic mice generated by crossing mice expressing human PSEN1 with the A246E mutation under the control of the mouse prion protein promoter with mice expressing chimeric APP (isoform 695) with the Swedish mutation also under the control of the mouse prion promoter. The chimeric APP molecule was created by replacing the mouse Aβ sequence with the cognate human sequence.

Phenotype Timeline

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Observed

Absent

  • Tangles
  • Neuronal Loss

Unknown

  • Cognitive Impairment

Plaques

Elevated Aβ42(43) peptide in the brain. By 9 months develop amyloid deposits in the cortex and hippocampus which become more numerous by 10-12 months (Borchelt et al., 1997). Aβ42 and Aβ40 codeposit (Jankowsky et al., 2004).

Tangles

Absent.

Neuronal Loss

No difference in neuronal numbers in the cingulate cortex compared with wild-type animals (Xiang et al., 2002).

Gliosis

Reactive gliosis in the cortex and hippocampus associated with dystrophic neurites (Borchelt et al., 1997).

Cognitive Impairment

Unknown.

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References

Research Models Citations

  1. APPSwe (line C3-3)

Paper Citations

  1. . Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron. 1997 Oct;19(4):939-45. PubMed.
  2. . Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet. 2004 Jan 15;13(2):159-70. Epub 2003 Nov 25 PubMed.

External Citations

  1. The Jackson Lab: Stock# 003378

Further Reading

No Available Further Reading