Species: Mouse
Genes: APP, MAPT, PSEN2
Mutations: APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN2 N141I
Modification: APP: Transgenic; MAPT: Transgenic; PSEN2: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: B6.D2-Tg(Thy1-APPSwe, Prp-PSEN2N141I, Thy1-TauP301L)
Genetic Background: C57BL/6, DBA/2; backcrossed to C57BL/6
Availability: Available through Laurence Ozmen

Summary

These triple transgenic mice express mutant APP, PSEN2, and MAPT. They show age-dependent accumulation of Aβ plaques and neurofibrillary tangle-like pathology, starting around four months of age (Grueninger et al., 2010).

Neuropathology

Phosphorylated tau accumulates in the subiculum and the CA1 region of the hippocampus at four months. Neurofibrillary tangles also appear in these regions as well as the amygdala. Dystrophic neurites have also been observed along with neuropil threads containing abnormally phosphorylated tau. No overt neuronal loss. Amyloid plaques (Grueninger et al., 2010).

Cognition/Behavior

Impaired spatial learning in the Morris water maze at four months, but impairment is not progressive between four and twelve months and appears to be independent of pathology (Grueninger et al., 2010).

Other Phenotypes

Cortex-specific deficiencies in oxidative phosphorylation. Loss of mitochondrial membrane potential. Reduced cortical ATP. Increased superoxide anions and reactive oxygen species compared to wild-type controls (Rhein et al., 2009). No differences in APP expression, APP cleavage or Aβ accumulation compared to the double transgenic mouse PS2APP. Levels of tau phosphorylated at serine 422 increased in an age-dependent manner, but levels of tau phosphorylated at threonine 231 did not (Grueninger et al., 2010).

Modification Details

These animals were generated by crossing homozygous PS2APP mice (line B6.152H) to hemizygous tau mice (line B6.TauP301L). PS2APP were generated by co-injecting two transgenic constructs: human PSEN2 (N141I mutation) and human APP (Swedish mutation) driven by the mouse prion promoter and the mouse Thy1 promoter respectively (Ozmen et al., 2009). The transgenic TauP301L mouse (line pR5) expresses the human tau40 isoform driven by the Thy1.2 promoter (Kins et al., 2001).

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

Paper Citations

1. 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.
2. Rhein V, Song X, Wiesner A, Ittner LM, Baysang G, Meier F, Ozmen L, Bluethmann H, Dröse S, Brandt U, Savaskan E, Czech C, Götz J, Eckert A. Amyloid-beta and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice. Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20057-62. PubMed.
3. 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.
4. Kins S, Crameri A, Evans DR, Hemmings BA, Nitsch RM, Gotz J. Reduced protein phosphatase 2A activity induces hyperphosphorylation and altered compartmentalization of tau in transgenic mice. J Biol Chem. 2001 Oct 12;276(41):38193-200. Epub 2001 Jul 25 PubMed.

Other Citations

1. Laurence Ozmen

Further Reading