Updated 30 March 2010

General Information

Transgene: Human APP cDNA clone (3'-UTR extended to SmaI at +3100) with the Arctic mutation (E693G) and with the Swedish mutation (KM670/671NL) was generated, attached to a modified Kozak sequence, inserted into the murine Thy-1 promoter and sequenced. The construct was linearized with NotI and purified with β-agarase, microinjected (2 μg/ml) into pronuclear oocytes of C57BL/6-CBA-F1 mice and implanted into pseudopregnant foster mothers at the two-cell stage.

Mutation: Arctic mutation (E693G) and Swedish mutation (KM670/671NL)

Promoter: Murine Thy-1 promoter

Mouse Strain: C57BL/6J-CBA-F1; C57BL/6J-CBA; C57Bl/6J; C57Bl/6J, (backcrossed for five generations)

Phenotype

Neuropathological Analysis:

Strong intraneuronal Aβ aggregation which is associated with an early onset of extracellular amyloid deposition at around 5-6 months of age. Cerebrovascular amyloid angiopathy (CAA) is present, mainly in the thalamus and cerebral cortex, but congophilic parenchymal plaque depositon is the dominating neuropathological feature. Dissolution of Aβ deposits requires formic acid, like in postmortem Alzheimer's disease brain.

The inclusion of the Artic mutation in the transgene results in enhanced accumulation of soluble Aβ aggregates, such as Aβ protofibrils, facilitated accumulation of Aβ inside neurons and more robust senile plaques.

Behavioral Phenotype:

Spatial learning deficits at 4-8 months of age in Morris water maze.

Availability

Non-commercial use:
Lars Nilsson, lars.nilsson@pubcare.uu.se
Department of Public Health and Caring Sciences
Rudbeck Laboratory, Molecular Geriatrics
Uppsala University, Sweden

Reference

Primary:

Lord A, Kalimo H, Eckman C, Zhang X-O, Lannfelt L, Nilsson LNG. The Arctic Alzheimer mutation facilitates early intraneuronal Abeta aggregation and senile plaque formation in transgenic mice. Neurobiol. Aging. 2006; 27(1):67-77. Abstract

Associated:

Sahlin C, Lord A, Magnusson K, Englund H, Almeida CG, Greengard P, Nyberg F, Gouras GK, Lannfelt L, Nilsson LN. The Arctic Alzheimer mutation favors intracellular amyloid-beta production by making amyloid precursor protein less available to alpha-secretase. J Neurochem. 2007 May 1;101(3):854-62. Abstract

Englund H, Sehlin D, Johansson AS, Nilsson LN, Gellerfors P, Paulie S, Lannfelt L, Pettersson FE. Sensitive ELISA detection of amyloid-beta protofibrils in biological samples. J Neurochem. 2007 Oct 1;103(1):334-45. Abstract

Philipson O, Hammarström P, Nilsson KP, Portelius E, Olofsson T, Ingelsson M, Hyman BT, Blennow K, Lannfelt L, Kalimo H, Nilsson LN. A highly insoluble state of Abeta similar to that of Alzheimer's disease brain is found in Arctic APP transgenic mice. Neurobiol Aging. 2008 Jan 11; Abstract