- 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.
- 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.
- 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.
Orders by weight:
- 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.
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.
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