Research Models

APP(Swedish) (R1.40)

Synonyms: APPK670/M671, R1.40-YAC

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Species: Mouse
Genes: APP
Mutations: APP K670_M671delinsNL (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: The Jackson Lab; available through the JAX MMRRC Stock# 034831; Cryopreserved

Summary

These transgenic mice express mutant human APP with the Swedish mutation. R1.40 mice contain six to eight copies of the mutant APP YAC and express human APP at approximately two to three-fold 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).

This model was previously available through The Jackson Lab as Stock# 005300.

Modification Details

A 650 kb YAC transgene containing the entire human APP gene and about 250 kb of flanking sequence was mutated to include the Swedish mutation (K670N/M671L). Founder animals (line R1.40) were backcrossed to C57BL/6J.

Related Strains

129S1.129(Cg)-Tg(APPsw)40Btla/Mmjax
The Jackson Lab; the JAX MMRRC Stock# 034838 (formerly The Jackson Lab Stock# 006409)

A.129(B6)-Tg(APPSw)40Btla/Mmjax The Jackson Lab; the JAX MMRRC Stock# 034841 (formerly The Jackson Lab Stock# 006555)

D2.129(B6)-Tg(APPSw)40Btla/Mmjax
The Jackson Lab; the JAX MMRRC Stock# 034839 (formerly The Jackson Lab Stock# 006472)

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).

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Absent

  • Tangles
  • Changes in LTP/LTD

No Data

  • Neuronal Loss
  • Synaptic Loss
  • Cognitive Impairment

Plaques

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).

Tangles

No mature tangles, but some changes in phosphorylated tau.

Neuronal Loss

Unknown.

Gliosis

Reactive astrocytes and microglia in 14-16 month old animals (Kulnane et al., 2001).

Synaptic Loss

Unknown.

Changes in LTP/LTD

Absent.

Cognitive Impairment

Unknown.

Last Updated: 25 Nov 2019

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References

Paper Citations

  1. 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.
  2. 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.
  3. 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.

External Citations

  1. The Jackson Lab; the JAX MMRRC Stock# 034838
  2. The Jackson Lab; the JAX MMRRC Stock# 034841
  3. The Jackson Lab; the JAX MMRRC Stock# 034839
  4. JAX MMRRC Stock# 034831

Further Reading

Papers

  1. Varvel NH, Bhaskar K, Patil AR, Pimplikar SW, Herrup K, Lamb BT. Abeta oligomers induce neuronal cell cycle events in Alzheimer's disease. J Neurosci. 2008 Oct 22;28(43):10786-93. PubMed.
  2. Ryman D, Gao Y, Lamb BT. Genetic loci modulating amyloid-beta levels in a mouse model of Alzheimer's disease. Neurobiol Aging. 2008 Aug;29(8):1190-8. PubMed.
  3. Ryman D, Lamb BT. Genetic and environmental modifiers of Alzheimer's disease phenotypes in the mouse. Curr Alzheimer Res. 2006 Dec;3(5):465-73. PubMed.
  4. Lehman EJ, Kulnane LS, Gao Y, Petriello MC, Pimpis KM, Younkin L, Dolios G, Wang R, Younkin SG, Lamb BT. Genetic background regulates beta-amyloid precursor protein processing and beta-amyloid deposition in the mouse. Hum Mol Genet. 2003 Nov 15;12(22):2949-56. Epub 2003 Sep 23 PubMed.