Research Models

APPSwe/PSEN1dE9

Synonyms: APPSwe(line C3-3) X PS1dE9 (line S-9), C3-3/PS1-dE9, C3-3 x S-9

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Species: Mouse
Genes: APP, PSEN1
Mutations: APP KM670/671NL (Swedish), PSEN1: deltaE9
Modification: APP: Transgenic; PSEN1: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/J
Genetic Background: Line C3-3: C57BL/6J; Line S-9: hybrid strain C3H/HeJ;C57BL/6J) backcrossed to C57BL/6J
Availability: The Jackson Lab, available through the JAX MMRRC Stock# 034833; Live

Summary

These double transgenic mice were created by breeding mice that express mutant APP (line C3-3) with mice that express mutant PSEN1 (line S-9). Line C3-3 mice express a chimeric mouse/human APP (isoform 695) which is driven by the mouse prion promoter. The Swedish mutation was introduced into the APP sequence in order to increase total Aβ generation (Borchelt et al., 1996; Savonenko et al., 2003). Line S-9 mice (Lee et al., 1997) express human PSEN1 lacking exon 9, which models the AD-associated mutations involving deletion of exon 9, variously known as ΔE9, dE9, deltaE9, Δ9, or delE9.

The double transgenic mice are viable and fertile. Unlike C3-3 single transgenic mice, which do not develop amyloid deposits until beyond 18 months of age (Borchelt et al., 1997), the double transgenic mice have visible plaque deposition at six months of age with an even greater amyloid burden at 18 months. Cognitive impairment occurs subsequent to plaque deposition; APPSwe/PSEN1dE9 mice are indistinguishable from nontransgenic mice on cognitive tasks at six months, but by 18 months perform less well than either single transgenics or wild-type animals (Savonenko et al., 2005).

Some AD patients with ΔE9 mutations develop neuropathology that is atypical for AD, including large "cotton wool" amyloid deposits in the cortex with a relative absence of compact dense core plaques. APPSwe/PSEN1dE9 mice, however, do not display cotton wool plaques, but instead have compact dense core deposits typical of AD (Jankowsky et al., 2004).

This model was previously available through The Jackson Lab as Stock# 005866.

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References

Research Models Citations

  1. APPSwe (line C3-3)

Paper Citations

  1. . A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet Anal. 1996 Dec;13(6):159-63. PubMed.
  2. . Normal cognitive behavior in two distinct congenic lines of transgenic mice hyperexpressing mutant APP SWE. Neurobiol Dis. 2003 Apr;12(3):194-211. PubMed.
  3. . Hyperaccumulation of FAD-linked presenilin 1 variants in vivo. Nat Med. 1997 Jul;3(7):756-60. PubMed.
  4. . 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.
  5. . Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities. Neurobiol Dis. 2005 Apr;18(3):602-17. PubMed.
  6. . 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. JAX MMRRC Stock# 034833

Further Reading

No Available Further Reading