Research Models

Arc48 (APPSw/Ind/Arc)

Synonyms: APPSwedish/Indiana/Arctic, hAPP Arc line

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Species: Mouse
Genes: APP
Mutations: APP KM670/671NL (Swedish), APP V717F (Indiana), APP E693G (Arctic)
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease, Cerebral Amyloid Angiopathy
Strain Name: N/A
Genetic Background: Inbred C57BL/6
Availability: Cryopreserved. Contact Lennart Mucke

Modification Details

A human APP minigene with the Swedish, Indiana, and Arctic mutations driven by the platelet-derived growth factor β-chain promoter.

Neuropathology

Parenchymal neuritic plaques by two months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by three to four months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20 (Cheng et al., 2004; Cheng et al., 2007).

Cognition/Behavior

At three to four months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to find the hidden platform (Cheng et al., 2007).

Other Phenotypes

Premature lethality. Trend toward hyperactivity. Reduced calbindin and Fos levels in the dentate gyrus (Cheng et al., 2007).

Note

The Arc48 line was generated in conjunction with a second line (Arc6) carrying the same mutant APP minigene. Arc48 had higher transgene expression than Arc6, and more severe pathology (Cheng et al., 2004). These two Arc lines have been characterized in relation to J20 mice which express a human APP minigene containing the Swedish and Indiana mutations. In the forbrain, the relative expression of APP in these three lines is: Arc48>J20>Arc6 (Cheng et al., 2007).

Availability

Cryopreserved. Contact Lennart Mucke.

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

Unknown

  • Neuronal Loss
  • Synaptic Loss
  • Changes in LTP/LTD

Plaques

Parenchymal neuritic plaques by 2 months with prominent plaque deposition in the hippocampus by 3-4 months. Abundant mature thioflavin-S positive plaques with dystrophic neurites by 10-12 months (Cheng et al., 2007).

Tangles

Absent.

Neuronal Loss

Unknown.

Gliosis

Reactive astrocytosis at 3-4 months in the dentate gyrus as demonstrated by GFAP immunoreactivity (Cheng et al., 2007).

Synaptic Loss

Unknown.

Changes in LTP/LTD

Unknown.

Cognitive Impairment

At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but were impaired in the ability to use extramaze cues to navigate to the hidden platform (Cheng et al., 2007).

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Comments

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References

Research Models Citations

  1. J20 (PDGF-APPSw,Ind)

Paper Citations

  1. . Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation. Nat Med. 2004 Nov;10(11):1190-2. PubMed.
  2. . Accelerating amyloid-beta fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. J Biol Chem. 2007 Aug 17;282(33):23818-28. PubMed.

Other Citations

  1. Lennart Mucke

External Citations

  1. J20

Further Reading

No Available Further Reading