Age-Dependent Neurofibrillary Tangle Formation, Neuron Loss, and Memory Impairment in a Mouse Model of Human Tauopathy (P301L)

Here, we describe the generation of a novel transgenic mouse model of human tauopathy. The rTg(tau(P301L))4510 mouse expresses the P301L mutation in tau (4R0N) associated with frontotemporal dementia and parkinsonism linked to chromosome 17. Transgene expression was driven by a forebrain-specific Ca(2+) calmodulin kinase II promoter system resulting in high levels of expression in the hippocampus and neocortex. Importantly, transgene expression in this model is induced via the tetracycline-operon responsive element and is suppressed after treatment with doxycycline. Continued transgene expression in rTg(tau(P301L))4510 mice results in age-dependent development of many salient characteristics of hereditary…

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  National Institutes of Health