Mutations: APP KM670/671NL (Swedish)
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: B6.129-Tg(APPSw)40Btla/Mmjax
Genetic Background: (129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Availability: Jackson Labs: Stock# 005300; Cryopreserved
A 650kb YAC transgene containing the entire human APP gene and ~250kb of flanking sequence was mutated to include the Swedish mutation (K670N/M671L). Founder animals (line R1.40) were backcrossed to C57BL/6J.
These transgenic mice express mutant human APP with the Swedish mutation. R1.40 mice contain 6-8 copies of the mutant APP YAC and express human APP at approximately 2-3x higher levels than the level of endogenous mouse APP (Lamb et al., 1997). By 14-16 months, homozygotes show diffuse and compact Aβ deposits in the frontal cortex; by 18-20 months plaques extend throughout the cortex and into the olfactory bulb with occasional deposits in the corpus callosum and hippocampus. No tangles have been observed, but changes in phosphorylated tau have been noted. Reactive astrocytes and microglia are observed by 14-16 months associated with plaques. Apoptosis is not characteristic of this model (Kulnane et al., 2001).
Jackson Labs Stock# 006409 129S1.129(Cg)-Tg(APPsw)40Btla/Mmjax
Jackson Labs Stock# 006555 A.129(B6)-Tg(APPSw)40Btla/Mmjax
Jackson Labs Stock# 006472 D2.129(B6)-Tg(APPSw)40Btla/Mmjax
Note: The phenotypes in these lines vary. Differences are observed in the levels of brain APP C-terminal fragments (CTFs), brain and plasma levels of Aβ40 and Aβ42 (B6-R1.40> 129S1-R1.40> D2-R1.40), and the extent and age of onset of Aβ deposition (Lehman et al., 2003).
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
- Changes in LTP/LTD
- Neuronal Loss
- Synaptic Loss
- Cognitive Impairment
By 13.5 months homozygous mice develop both parenchymal and vascular amyloid deposits which first appear in the frontal cortex. No Aβ deposition at 5 months (Lehman et al., 2003).
No mature tangles, but some changes in phosphorylated tau.
Reactive astrocytes and microglia in 14-16 month old animals (Kulnane et al., 2001).
Changes in LTP/LTD
- 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.
- Kulnane LS, Lamb BT. Neuropathological characterization of mutant amyloid precursor protein yeast artificial chromosome transgenic mice. Neurobiol Dis. 2001 Dec;8(6):982-92. PubMed.
- Lehman EJ, Kulnane LS, Lamb BT. Alterations in beta-amyloid production and deposition in brain regions of two transgenic models. Neurobiol Aging. 2003 Sep;24(5):645-53. PubMed.
No Available Further Reading