Mutations: APP KM670/671NL
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: C3B6-Tg(APP695)3Dbo/Mmjax
Genetic Background: C3H/HeJ x C57BL/6J; backcrossed to C57BL/6J
Availability: The Jackson Lab; available through the JAX MMRRC Stock# 034828; Cryopreserved
These transgenic mice express a chimeric mouse/human APP carrying the Swedish mutation under the control of the mouse prion protein promoter. This line, C3-3, was generated in parallel with line E1-2, which also expresses APP carrying the Swedish mutation. Mice that are hemizygous for the transgene are viable and fertile and express mutant human APP at levels about 3-fold higher than endogenous mouse APP. These mice do not exhibit amyloid plaque deposition until approximately 18 to 20 months of age (Borchelt et al., 1997; Janokowsky et al., 2004). They do not show impairments in standard working and reference memory tasks (Savonenko et al., 2003).
This model was previously available through The Jackson Lab as Stock# 003375.
The transgene is a chimeric mouse/human APP (isoform 695) with a "humanized" Aβ domain and the Swedish mutation under the control of the mouse prion protein promoter.
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
- Cognitive Impairment
- Neuronal Loss
- Synaptic Loss
- Changes in LTP/LTD
Some plaque formation at advanced age (24-26 months) (Savonenko et al., 2003).
Changes in LTP/LTD
Normal reference and working memory up to 12-14 months on congenic background (Savonenko et al., 2003).
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.
- Savonenko AV, Xu GM, Price DL, Borchelt DR, Markowska AL. Normal cognitive behavior in two distinct congenic lines of transgenic mice hyperexpressing mutant APP SWE. Neurobiol Dis. 2003 Apr;12(3):194-211. PubMed.