Nomenclature: C57BL/6NTac.CBA-Tg(Thy1-PSEN1*M146V,-APP*Swe)10Arte

• 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.

• 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.

Origin