Genes: APP, PSEN1
Mutations: APP KM670/671NL (Swedish), PSEN1 A246E
Modification: APP: Transgenic; PSEN1: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J
Genetic Background: Origin: (C57BL/6J x C3H/HeJ)F2
Availability: The Jackson Lab: Stock# 003378; Cryopreserved
These double transgenic mice were created by breeding mice which express the human PSEN1 gene carrying the A246E mutation with mice expressing a chimeric APP protein with the Swedish mutation (see APPSwe line C3-3). These mice exhibit elevated Aβ42(43) peptide in the brain, and by nine months develop numerous amyloid deposits which increase dramatically in number between ten and twelve months of age (Borchelt et al., 1997). Aβ42 and Aβ40 codeposit (Jankowsky et al., 2004).
These are double transgenic mice generated by crossing mice expressing human PSEN1 with the A246E mutation under the control of the mouse prion protein promoter with mice expressing chimeric APP (isoform 695) with the Swedish mutation also under the control of the mouse prion promoter. The chimeric APP molecule was created by replacing the mouse Aβ sequence with the cognate human sequence.
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
- Neuronal Loss
- Cognitive Impairment
Elevated Aβ42(43) peptide in the brain. By 9 months develop amyloid deposits in the cortex and hippocampus which become more numerous by 10-12 months (Borchelt et al., 1997). Aβ42 and Aβ40 codeposit (Jankowsky et al., 2004).
No difference in neuronal numbers in the cingulate cortex compared with wild-type animals (Xiang et al., 2002).
Reactive gliosis in the cortex and hippocampus associated with dystrophic neurites (Borchelt et al., 1997).
Research Models Citations
- Borchelt DR, Ratovitski T, van Lare J, Lee MK, Gonzales V, Jenkins NA, Copeland NG, Price DL, Sisodia SS. Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron. 1997 Oct;19(4):939-45. PubMed.
- Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, Lee MK, Younkin LH, Wagner SL, Younkin SG, Borchelt DR. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet. 2004 Jan 15;13(2):159-70. Epub 2003 Nov 25 PubMed.
No Available Further Reading