- 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.
- Gender 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.
Availability: Young inventory available now in typical study sizes. Limited quantities of aged inventory (18-50 weeks of age) available - please
inquire for details.
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 is currently being backcrossed to C57BL/6NTac. All animals in the current inventory are expected to be no less than 98% of C57BL/6 strain background. This will increase as the backcross progresses to completion and refreshes the production colony. Upon completion of the backcross and production colony refreshment, animals are expected to be no less than 99.9% C57BL/6 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.
