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,Prnp-PSEN2*N141I)152HLaoz
Genetic Background: C57BL/6
Availability: Available through Laurence Ozmen

Summary

There are two mouse models referred to by the name “PS2APP” to in the literature. This entry refers to the model that was generated by co-injecting two constructs into C57/BL/6 zygotes, and is also known by the name B6.152H. The other PS2APP line was generated by crossing two single transgenic animals (PS2(N141I) x APPswe) (Richards et al., 2003). Both lines of double transgenic animals express the same transgenes and both develop a similar level of cerebral pathology (Weidensteiner et al., 2009), but only the B6.152H mice show enhanced LTP. The reasons for this are not entirely clear, but differing levels of transgene expression may be partly responsible. B6.152H mice have higher expression of transgenic human APP mRNA (1.45-fold) compared to PS2APP mice and approximately 30-fold higher levels of PSEN2 mRNA. They also have about 2-fold higher Aβ levels than PS2APP mice (Poirier et al., 2010). The B6.152H line is maintained as a homozygote line. It is on a pure C57BL/6 background and shows less variability in pathology expression. It has been used to generate the TauPS2APP triple transgenic line by crossing with the Tau-overexpressing pR5 line (Grueninger et al., 2010).

Modification Details

Coinjection of two transgenes into C57/BL/6 zygotes: human PSEN2 with the N141I mutation driven by the mouse prion protein promoter and human APP (isoform 751) with the Swedish mutation driven by the Thy1.2 promoter.

Neuropathology

Age-associated development of plaques: none at 3 months, overt Aβ deposition in the brain at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months. Aβ deposits in blood vessels were sporadic, mainly in large vessels. The amount of cerebral amyloid deposits correlated with levels of the human APP transcript at 12 months (Ozmen et al., 2009; Weidensteiner et al., 2009).

Cognition/Behavior

Cognitive impairment detected by the Morris water maze at eight and 12 months of age, not at three months (personal communication, Laurence Ozmen).

Other Phenotypes(s)

Decreased survival of newborn neurons in the dentate gyrus at about four months compared to wild-type (Poirier et al., 2010). Compared with neurons isolated from wild-type mice, neurons from mutant mice show reduced endoplasmic reticulum Ca²⁺ and calcium dysregulation (Kipanyula et al., 2012). A strong increase in LTP and post-tetanic potentiation (PTP) in hippocampal slices of ten month-old animals compared to wild-type mice (Poirier et al., 2010). Decreased perfusion in the occipital cortex at all ages tested (10-17 months) (Weidensteiner et al., 2009).

Availability

Available through Laurence Ozmen.

Phenotype Characterization

COMMENTS / QUESTIONS

No Available Comments

Make a comment or submit a question

To make a comment you must login or register.

References

Research Models Citations

1. PS2APP (PS2(N141I) x APPswe)
2. TauPS2APP

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. Weidensteiner C, Metzger F, Bruns A, Bohrmann B, Kuennecke B, von Kienlin M. Cortical hypoperfusion in the B6.PS2APP mouse model for Alzheimer's disease: comprehensive phenotyping of vascular and tissular parameters by MRI. Magn Reson Med. 2009 Jul;62(1):35-45. PubMed.
3. Poirier R, Veltman I, Pflimlin MC, Knoflach F, Metzger F. Enhanced dentate gyrus synaptic plasticity but reduced neurogenesis in a mouse model of amyloidosis. Neurobiol Dis. 2010 Nov;40(2):386-93. PubMed.
4. Grueninger F, Bohrmann B, Czech C, Ballard TM, Frey JR, Weidensteiner C, von Kienlin M, Ozmen L. Phosphorylation of Tau at S422 is enhanced by Abeta in TauPS2APP triple transgenic mice. Neurobiol Dis. 2010 Feb;37(2):294-306. PubMed.
5. 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.
6. Kipanyula MJ, Contreras L, Zampese E, Lazzari C, Wong AK, Pizzo P, Fasolato C, Pozzan T. Ca(2+) dysregulation in neurons from transgenic mice expressing mutant presenilin 2. Aging Cell. 2012 Oct;11(5):885-93. PubMed.

Other Citations

1. Laurence Ozmen

Further Reading