Mutations: APP KM670/671NL (Swedish), APP V717I (London)
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: B6.129S4-Tg(APPSwLon)96Btla/Mmjax
Genetic Background: 129S4/SvJae-derived J1 ES cells; backcrossed to C57BL/6
Availability: Jackson Labs: Stock# 006406; Cryopreserved
A 650 kb YAC transgene containing the entire human APP gene carrying the Swedish and London mutations with ~ 250 kb of flanking sequence.
These mice express human APP with the Swedish (K670N/M671L) and London (V717I) mutations. Founder animals (line J1.96) contained a single copy of transgene. Hemizygous animals are viable and fertile and express mutant human APP mRNA at levels comparable to those of endogenous mouse mRNA in the brain and periphery. They express APP 695, 751 and 770 transcripts (Lamb et al., 1997). At 3-4 months hemizygous animals were found to generate Aβ42 at levels 2-3x higher than those of wild-type APP YAC transgenic mice, and levels in homozygous animals were 4-6x higher than those in hemizygous wild-type APP YAC transgenic mice, but no amyloid deposits were observed at 2 years (Lamb et al., 1999).
- Lamb BT, Call LM, Slunt HH, Bardel KA, Lawler AM, Eckman CB, Younkin SG, Holtz G, Wagner SL, Price DL, Sisodia SS, Gearhart JD. Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice. Hum Mol Genet. 1997 Sep;6(9):1535-41. PubMed.
- Lamb BT, Bardel KA, Kulnane LS, Anderson JJ, Holtz G, Wagner SL, Sisodia SS, Hoeger EJ. Amyloid production and deposition in mutant amyloid precursor protein and presenilin-1 yeast artificial chromosome transgenic mice. Nat Neurosci. 1999 Aug;2(8):695-7. PubMed.
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