Species: Mouse
Genes: APP, PSEN2
Mutations: APP K670_M671delinsNL (Swedish), PSEN2 N141I
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).

The parental origin of the transgenes was shown to influence AD-related pathology in another model, 5xFAD (C57BL6), in which the Thy1 promoter drives transgene expression, possibly due to genomic imprinting of the promoter (Sasmita et al., 2025). While this phenomenon has not yet been demonstrated in PS2APP (PS2(N141I) x APPswe) mice, users of this model should be aware of the findings in 5xFAD mice when designing and documenting breeding strategies.

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 Characterization

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References

Research Models Citations

1. PS2(N141I)
2. APPSwe
3. PS2APP
4. 5xFAD (C57BL6)

Paper Citations

1. Richards JG, Higgins GA, Ouagazzal AM, Ozmen L, Kew JN, Bohrmann B, Malherbe P, Brockhaus M, Loetscher H, Czech C, Huber G, Bluethmann H, Jacobsen H, Kemp JA. 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. Ozmen L, Albientz A, Czech C, Jacobsen H. 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. Sasmita AO, Ong EC, Nazarenko T, Mao S, Komarek L, Thalmann M, Hantakova V, Spieth L, Berghoff SA, Barr HJ, Hingerl M, Börensen F, Hirrlinger J, Simons M, Stevens B, Depp C, Nave KA. Parental origin of transgene modulates amyloid-β plaque burden in the 5xFAD mouse model of Alzheimer's disease. Neuron. 2025 Jan 20; Epub 2025 Jan 20 PubMed.
4. Richards G, Messer J, Faull RL, Stadler H, Wichmann J, Huguenin P, Bohrmann B, Mutel V. 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