Research Models

PS2APP (PS2(N141I) x APPswe)

Synonyms: hPS2(N141I) x hAPPswe

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Species: Mouse
Genes: APP, PSEN2
Mutations: APP KM670/671NL (Swedish), PSEN2 N141I (Volga German)
Modification: APP: Transgenic; PSEN2: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: Tg(Thy1-APPSwe)71Jgr x Tg(Prnp-PSEN2*N141I)30Jgr
Genetic Background: C57BL/6, DLB/2, crossed to C57BL/6
Availability: Available through Laurence Ozmen.

Summary

There are two mouse models commonly called "PS2APP" in the literature. This entry refers to the model that was generated by crossing two single transgenic animals (PS2(N141I) x APPswe) (Richards et al., 2003). The other PS2APP model relies on the same genetic constructs, but rather than crossing two transgenic lines, the constructs were co-injected into C57/BL/6 zygotes (Ozmen et al., 2009). The latter model is maintained as a homozygote line, is in a pure C57BL/6 background, and shows less variability in pathology.

Modification Details

Double transgenics created by crossing APPSwe mice (human APP751 with the Swedish mutation driven by the Thy1.2 promoter) with PS2(N141I) mice (human PSEN2 with the N141I mutation driven by the mouse prion protein promoter).

Neuropathology

Rare amyloid deposits are detectable at five months, with consistent deposits appearing in the subiculum and frontolateral cortex by nine months. Plaques increase in number and distribution with time, spreading throughout the neocortex and hippocampus as well as the amygdala, thalamus, and pontine nuclei. The distribution and abundance of activated microglia and astrocytes correlate with Aβ deposition (Richards et al., 2003).

Cognition/Behavior

Mice develop age-associated cognitive impairment from eight months with impaired acquisition of spatial learning in the water maze (Richards et al., 2003).

Other Phenotypes

More insoluble Aβ40 and Aβ42 than age-matched APPSwe mice at 16-18 months (Richards et al., 2003). Loss of metabotropic glutamate (mGlu2) receptors in certain brain regions of aged PS2APP mice as demonstrated by autoradiography (Richards et al., 2010).

Availability

Frozen embryos available through Laurence Ozmen.

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
  • Changes in LTP/LTD

Unknown

  • Neuronal Loss
  • Synaptic Loss

Plaques

Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution over time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei (Richards et al., 2003).

Tangles

Absent.

Neuronal Loss

Unknown.

Gliosis

An inflammatory response indicated by the presence of activated microglia and astrocytes begins around 9 months. The onset, distribution, and abundance of activated microglia and astrocytes correlate with Aβ deposition.

Synaptic Loss

Unknown.

Changes in LTP/LTD

No difference in LTP in the dentate gyrus at 3 and 10 months compared to wild-type mice (Richards et al., 2003).

Cognitive Impairment

Age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze (Richards et al., 2003).

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References

Research Models Citations

  1. PS2(N141I)
  2. APPSwe
  3. PS2APP

Paper Citations

  1. . PS2APP transgenic mice, coexpressing hPS2mut and hAPPswe, show age-related cognitive deficits associated with discrete brain amyloid deposition and inflammation. J Neurosci. 2003 Oct 1;23(26):8989-9003. PubMed.
  2. . Expression of transgenic APP mRNA is the key determinant for beta-amyloid deposition in PS2APP transgenic mice. Neurodegener Dis. 2009;6(1-2):29-36. PubMed.
  3. . Altered distribution of mGlu2 receptors in β-amyloid-affected brain regions of Alzheimer cases and aged PS2APP mice. Brain Res. 2010 Dec 2;1363:180-90. PubMed.

Other Citations

  1. Laurence Ozmen

Further Reading

Papers

  1. . Ca(2+) dysregulation in neurons from transgenic mice expressing mutant presenilin 2. Aging Cell. 2012 Oct;11(5):885-93. PubMed.