- Transgenic line with two co-integrated constructs: Thy-1 promoter specific expression the transgene coding for the 695-amino acid isoform that harbors the Swedish mutation of human Alzheimer β-amyloid (Aβ) precursor protein, as well as human Presenilin 1 carrying the M146V mutation (PS1M146V).
- Expresses high concentrations of human Aβ protein and develops human AD-like amyloid pathology due to genetic mutations within the human APP and PSEN1 genes. Aβ42 is the predominant insoluble species in this model.
Application:- ARTE10 is an appropriate preclinical model for prolonged evaluation of amyloid-lowering therapies and has been successfully PET imaged in vivo and ex vivo using Pittsburgh compound B (PiB) tracers.
Aβ Pathology:- This model develops cerebral β-amyloidosis that mimics several β-amyloid characteristics of human AD neuropathology, which is associated with glial inflammation. The neuropathology is reported to progress rapidly and predictably, with up to 100%-penetrance and low inter-animal variability reported. In animals with advanced plaque deposition, cerebral amyloid angiopathy is also present.
- Pattern and sequence of Aβ deposition: Aβ plaque formation first occurs in the anterior neocortex and subiculum in both homozygous and hemizygous animals as early as 3-months and 5-months respectively.
- Quantification of Aβ plaque: Plaque load progressively increases with age of onset, rate, and maximum level of plaque deposition, which are transgene dose-related. Homozygous animals have higher amounts of both insoluble and soluble Aβ levels in the brain then hemizygous animals.
- Sex differences in either homo- or hemizygous animals with regards to Aβ pathology have not been reported in this line.
Note:- The homozygous & hemizygous ARTE10 animals are reported to possess a relatively low rate of premature mortality (15% and 0% at 12 months, respectively) with expected life expectancy beyond 20 months. At Taconic Biosciences, we have observed limited mortality post-weaning in the breeding colony, with some incidence of a tremor phenotype.
Orders by weight: Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation.
Genetic Background: C57BL/6 background. The ARTE10 model was backcrossed to C57BL/6NTac and refreshment of the production colony is in progress. All animals in the current inventory are expected to be no less than 98% of C57BL/6 strain background. This will increase as refreshment of the production colony progresses. Upon completion, animals are expected to be 100% congenic to the C57BL/6NTac genetic background.
Origin:
The ARTE10 mouse model was developed by Taconic in association with Evotec. The ARTE10 model was created by pronuclear co-injection of human cDNA constructs of Thy1-APPswe and Thy1-PS1M146V into B6CBF1 eggs and the founder line was selected based on amyloid plaque formation (Arte10-729). The two constructs were coinherited as a single transgene without segregation as assessed over several generations in backcrosses to C57BL/6. The colony is maintained via mating homozygous males and females. Genetics:
Wild type for Pde6brd1 mutation. Color:
Black Species:
Mouse Initial Publication:
Willuweit A.; Velden J.; Godemann R.; Manook A.; Jetzek F.; Tintrup H.; Kauselmann G.; Zevnik B.; Henriksen G.; Drzezga A.; Pohlner J.; Schoor M.; Kemp J.A.; von der Kammer H. (2009)
Early-Onset and Robust Amyloid Pathology in a New Homozygous Mouse Model of Alzheimer’s Disease.
PLoS ONE. 4 (11), e7931.
Other Publications:
- Manook, A.; Yousefi, B. H.; Willuweit, A.; Platzer, S.; Reder, S.; Voss, A.; Huisman, M.; Settles, M.; Neff, F.; Velden, J.; Schoor, M.; Kammer, H. V. D.; Wester, H.-J.; Schwaiger, M.; Henriksen, G.; Drzezga, A. Small-Animal PET Imaging of Amyloid-Beta Plaques with [11C]PiB and Its Multi-Modal Validation in an APP/PS1 Mouse Model of Alzheimers Disease. PLoS ONE 2012, 7 (3).
- Watanabe, T.; Hikichi, Y.; Willuweit, A.; Shintani, Y.; Horiguchi, T. FBL2 Regulates Amyloid Precursor Protein (APP) Metabolism by Promoting Ubiquitination-Dependent APP Degradation and Inhibition of APP Endocytosis. Journal of Neuroscience 2012, 32 (10), 3352–3365.
- Yousefi, B. H.; Manook André; Drzezga, A.; Reutern, B. V.; Schwaiger, M.; Wester Hans-Jürgen; Henriksen, G. Synthesis and Evaluation of11C-Labeled Imidazo[2,1-b]Benzothiazoles (IBTs) as PET Tracers for Imaging β-Amyloid Plaques in Alzheimer’s Disease. Journal of Medicinal Chemistry 2011, 54 (4), 949–956.
- Yousefi, B. H.; Drzezga, A.; Reutern, B. V.; Manook, A.; Schwaiger, M.; Wester, H.-J.; Henriksen, G. A Novel 18F-Labeled Imidazo[2,1-b]Benzothiazole (IBT) for High-Contrast PET Imaging of β-Amyloid Plaques. ACS Medicinal Chemistry Letters 2011, 2 (9), 673–677.
- Yousefi, B. H.; Manook, A.; Reutern, B. V.; Schwaiger, M.; Drzezga, A.; Wester, H.-J.; Henriksen, G. Development of an Improved Radioiodinated 2-Phenylimidazo[1,2-a]Pyridine for Non-Invasive Imaging of Amyloid Plaques. MedChemComm 2012, 3 (7), 775.
- Šišková, Z.; Justus, D.; Kaneko, H.; Friedrichs, D.; Henneberg, N.; Beutel, T.; Pitsch, J.; Schoch, S.; Becker, A.; Von Der Kammer, H.; Remy, S. Dendritic Structural Degeneration Is Functionally Linked to Cellular Hyperexcitability in a Mouse Model of Alzheimer’s Disease. Neuron 2014, 84 (5), 1023–1033.
