Impaired reversal learning of a food-rewarded four-arm spatial maze task observed at 8 months (Radde et al., 2006). Phenotype CharacterizationĬognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months (Serneels et al., 2009). The integration site is on lower arm of chromosome 2 between 40 and 60 cm. The human transgenes APP KM670/671NL and PSEN1 L166P are both under the control of the Thy1 promoter. Global neuronal loss is not observed in APPPS1 mice, but modest neuron loss was found in the granule cell layer of the dentate gyrus and other subregions with high neuron density at older ages, e.g. Impairments in LTP in the hippocampal CA1 region have also been reported to start around this age ( Gengler et al., 2010). Others have subsequently reported earlier observations of cognitive impairment, including deficits in the Morris Water maze at seven months of age ( Serneels et al., 2009). The first publication characterizing these mice reported that they exhibited impaired reversal learning of a food-rewarded four-arm spatial maze task at eight months of age ( Radde et al., 2006). CSF concentrations of total tau increase in these animals, starting at six months and reaching a 5-fold increase by 18 months of age. Aβ40 concentrations also decrease, but less dramatically (45 percent by 18 months). Aβ42 concentrations in CSF of these mice decrease with age, with a 50 percent reduction by six months of age and an 80 percent reduction by 18 months. The CSF levels of Aβ and tau have also been extensively examined in these mice ( Maia et al., 2013). Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen. Deposits appear in the hippocampus at about three to four months, and in the striatum, thalamus, and brainstem at four to five months. Amyloid plaque deposition starts at approximately six weeks of age in the neocortex. In the brain, the Aβ42/Aβ40 decreases with the onset of amyloid deposition ( Radde et al., 2006 Maia et al., 2013). Human Aβ42 is preferentially generated over Aβ40, but levels of both increase with age. In these mice, expression of the human APP transgene is approximately 3-fold higher than endogenous murine APP. Species: Mouse Genes: APP, PSEN1 Mutations: APP KM670/671NL (Swedish), PSEN1 L166P Modification: APP: Transgenic PSEN1: Transgenic Disease Relevance: Alzheimer's Disease Strain Name: B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr Genetic Background: C57BL/6J Availability: Available through Mathias Jucker SummaryĪPPPS1 mice contain human transgenes for both APP bearing the Swedish mutation and PSEN1 containing an L166P mutation, both under the control of the Thy1 promoter.

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