The PS19 transgenic mouse expresses the T34 isoform and 4 microtubule binding repeats (1N4R) of the tau protein with P301S mutation under the regulatory control of the murine prion promoter (Prnp). PS19 mice are a popular model to study tau aggregation, tauopathy and other symptoms of Alzheimer`s disease (University of Pennsylvania, USA; JAX 008169; Yoshiyama et al., 2007).
Animals present the following phenotype:
- Neuronal accumulation of phosphorylated tau and paired helical filaments (PHF) in different brain regions at 6 months (Yoshiyama et al., 2007)
- Cerebral atrophy and neuron loss at 12 months (Yoshiyama et al., 2007)
- Neuroinflammation observed as activated microglia and astrocytosis at 6 months and older (Yoshiyama et al., 2007; Lopez-Gonzalez et al., 2015)
- Muscle weakness and neurogenic muscular atrophy at 3 months (Yoshiyama et al., 2007)
- Reduced anxiety at 9 months (Briggs et al., 2017)
- Learning and memory deficits at 6 months (Takeuchi et al., 2011)
- Reduced survival (Yoshiyama et al., 2007)
Results from published efficacy studies show that many of these symptoms are partly reversible by different compounds:
- Survival, neuroinflammation, tau phosphorylation (Yoshiyama et al., 2007)
- Axonal dystrophy, learning and memory (Brunden et al., 2010)
- Brain atrophy, survival, nest building (DeVos et al., 2017)
The phenotype described above, relevant for AD and other neurodegenerative disorder, makes the PS19 mouse a perfect model for your drug testing.