Synonyms: APPSwedish/Indiana/Arctic, hAPP Arc line
Mutations: APP K670_M671delinsNL (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
A human APP minigene with the Swedish, Indiana, and Arctic mutations driven by the platelet-derived growth factor β-chain promoter.
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).
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).
Premature lethality. Trend toward hyperactivity. Reduced calbindin and Fos levels in the dentate gyrus (Cheng et al., 2007).
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).
Cryopreserved. Contact Lennart Mucke.
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
- Neuronal Loss
- Synaptic Loss
- Changes in LTP/LTD
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).
Reactive astrocytosis at 3-4 months in the dentate gyrus as demonstrated by GFAP immunoreactivity (Cheng et al., 2007).
Changes in LTP/LTD
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).
Last Updated: 20 Nov 2013
Research Models Citations
- Cheng IH, Palop JJ, Esposito LA, Bien-Ly N, Yan F, Mucke L. Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation. Nat Med. 2004 Nov;10(11):1190-2. PubMed.
- Cheng IH, Scearce-Levie K, Legleiter J, Palop JJ, Gerstein H, Bien-Ly N, Puoliväli J, Lesné S, Ashe KH, Muchowski PJ, Mucke L. 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.
No Available Further Reading
COMMENTS / QUESTIONS
No Available Comments
Make a comment or submit a question
To make a comment you must login or register.