Updated 30 March 2010
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
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.
Spatial learning deficits at 4-8 months of age in Morris water maze.
Lars Nilsson, firstname.lastname@example.org
Department of Public Health and Caring Sciences
Rudbeck Laboratory, Molecular Geriatrics
Uppsala University, Sweden
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.
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.
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