Objective: Our objective was to examine the effects of tau accumulation in transgenic mice, observing both motor function and behavior. 

Background: Tau hyper-phosphorylation is a critical factor in neurodegenerative diseases. To examine the effects of tau accumulation in a novel models of tauopathy we generated a transgenic mouse via modification of an existing strain that expresses the human P301L mutation of tau.

Methods: We bred hemizygous with hemizygous transgenic mice that express P301L tau under the control of a prion promoter (TauP301L). 

Results: Accumulation of hyper-phosphorylated tau (p-tau) in hemizygous mice was predominantly detected in the hippocampus, cortex, brainstem and thalamus, reminiscent of tau pathology in human progressive supranuclear palsy (PSP). TauP301L mice show a significant increase in both human and murine p-tau and display motor symptoms that mimic PSP. Homozygous mice are underweight and have severe motor symptoms and may live up to 6 months, while hemizygous mice live longer (up to 1.5 years) and look normal but begin to show anxiety-like behavior and progressive motor abnormalities resulting in paralysis from 6 months old. Daily treatment of these mice with low doses of the tyrosine kinase inhibitors Nilotinib or Bosutinib led to p-tau clearance and improvement in motor symptoms.

Conclusions: Accumulation of p-tau in the brainstem, cortex and thalamus leads to parkinsonian-like symptoms that mimic human PSP and tyrosine kinase inhibition reduces tau pathology and reverses Parkinsonism. 

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MDS Abstracts - https://www.mdsabstracts.org/abstract/tyrosine-kinase-inhibition-clears-tau-and-reserves-neuropathology-and-motor-symptoms-in-a-novel-model-of-progressive-supranuclear-palsy/