Conditional Tau Mouse Lines that Faithfully Recapitulate Alzheimer’s Disease-like Pathologies

Value Proposition: Effective therapy for Alzheimer’s disease (AD), the most common form of dementia and a devastating illness for the elderly, remains a great unmet need. For translational research and preclinical drug development, animal models that faithfully mimic the cardinal pathological features of AD are critical. A major limitation of current mouse models is the lack of progressive AD-like neuropathology, especially the severe age-dependent neuronal loss in their brains. In an effort to produce an improved model of the disease, we generated and characterized new mouse models that conditionally express the four repeat domain of human tau with the ΔK280 mutation (Tau4R-ΔK280 mice). The Tau4R-ΔK280 mice not only develop AD-like tau pathologies, but also recapitulate the age-dependent neuronal loss seen in AD. Advantages include:

• Transgenic mouse line conditionally expressing Tau4R-ΔK280 mimics salient features of AD
• Suitable for cross-breeding with APP mice to recapitulate key pathological features of AD as well as tauopathy
• Valuable tool for screening and discovery of novel AD therapeutics  

 
Technical Details: Johns Hopkins researchers have developed new lines of inducible Tau mice. The mice exhibit age- and dosage- dependent hyperphosphorylated tau aggregation with ensuing deposition of tau tangles, neuronal loss and forebrain atrophy. Importantly, deficits in working memory in these mouse models occur during the early stages of development of tauopathy. As observed in cases of AD, reactive astrogliosis is associated with severe neuronal loss in Tau4R-ΔK280 mice. Thus we have established a mouse model of tauopathy that mimic some salient features of AD. Crossbreeding of these mice with APP mice will create a mouse model showing tangles, plaques, neuronal loss and degeneration that will be useful for studying disease mechanisms and amenable for pre-clinical drug screening and validation of novel therapies for AD. 
 
Publication(s)/Associated Cases: Nat Commun. 2016 Jul 4;7:12082.

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