Research Models

APP(Swedish) (R1.40)

Synonyms: APP(K670/M671), R1.40-YAC

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

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.

Summary

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).

This model was formerly available through the Jackson Lab as Stock# 005300.

Related Strains
129S1.129(Cg)-Tg(APPsw)40Btla/Mmjax

The Jackson Lab; the JAX MMRRC Stock# 034838 (formerly Jackson Lab Stock# 006409)

A.129(B6)-Tg(APPSw)40Btla/Mmjax

The Jackson Lab; the JAX MMRRC Stock# 034841 (formerly Jackson Lab Stock# 006555)

D2.129(B6)-Tg(APPSw)40Btla/Mmjax

The Jackson Lab; the JAX MMRRC Stock# 034839 (formerly 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 Timeline

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

Observed

Absent

  • Tangles
  • Changes in LTP/LTD

Unknown

  • 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.

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References

Paper Citations

  1. . 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. . Neuropathological characterization of mutant amyloid precursor protein yeast artificial chromosome transgenic mice. Neurobiol Dis. 2001 Dec;8(6):982-92. PubMed.
  3. . 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

No Available Further Reading