Species: Mouse
Genes: PSEN1
Mutations: PSEN1 M146V
Modification: PSEN1: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: Swiss Webster x B6D2F1
Availability: Available through the Technology Transfer Office, Patents & Licensing, University of South Florida

Summary

Two lines of transgenic mice that overexpress PSEN1 with the M146V mutation were developed simulataneously (line 8.2 and line 8.9) (Duff et al., 1996). Both lines have been crossed  to Tg2576 animals to create PSAPP double transgenic animals (e.g. McGowan et al., 1999). In the original description of the PS1(M146V) model, it was reported that mice that overexpress mutant, but not wild-type PSEN1, show a selective increase in Aβ42(43). Overt neuropathology is absent in these mice up to 2.5 years (Duff et al., 1996). Altered mitochondrial activity and disregulation of calcium homeostasis are observed (Begley et al., 1999) as well as differences in electrophysiological function, namely, larger medium and late after hyperpolarizations in CA3 pyramidal cells compared with nontransgenic mice or those transgenic for wild-type PSEN1 (Barrow et al., 2000). Cognition has not been evaluated.

Modification Details

Transgene containing human PSEN1 with the M146V mutation driven by the rat PDGF-β promoter.

Availability

Available through the Technology Transfer Office, Patents & Licensing, University of South Florida.

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References

Paper Citations

1. Duff K, Eckman C, Zehr C, Yu X, Prada CM, Perez-Tur J, Hutton M, Buee L, Harigaya Y, Yager D, Morgan D, Gordon MN, Holcomb L, Refolo L, Zenk B, Hardy J, Younkin S. Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature. 1996 Oct 24;383(6602):710-3. PubMed.
2. McGowan E, Sanders S, Iwatsubo T, Takeuchi A, Saido T, Zehr C, Yu X, Uljon S, Wang R, Mann D, Dickson D, Duff K. Amyloid phenotype characterization of transgenic mice overexpressing both mutant amyloid precursor protein and mutant presenilin 1 transgenes. Neurobiol Dis. 1999 Aug;6(4):231-44. PubMed.
3. Begley JG, Duan W, Chan S, Duff K, Mattson MP. Altered calcium homeostasis and mitochondrial dysfunction in cortical synaptic compartments of presenilin-1 mutant mice. J Neurochem. 1999 Mar;72(3):1030-9. PubMed.
4. Barrow PA, Empson RM, Gladwell SJ, Anderson CM, Killick R, Yu X, Jefferys JG, Duff K. Functional phenotype in transgenic mice expressing mutant human presenilin-1. Neurobiol Dis. 2000 Apr;7(2):119-26. PubMed.

Other Citations

1. Tg2576

External Citations

1. Technology Transfer Office, Patents & Licensing, University of South Florida

Further Reading

No Available Further Reading