Knock-out and transgenic mouse models of tauopathies.
Denk F., Wade-Martins R.
Tauopathies, characterized by the dysfunction and aggregation of the microtubule-associated protein tau (MAPT), represent some of the most devastating neurodegenerative disorders afflicting the elderly, including Alzheimer's disease and progressive supranuclear palsy. Here we review the range of Mapt knock-out and MAPT transgenic mouse models which have proven successful at providing insights into the molecular mechanisms of neurodegenerative disease. In this overview we highlight several themes, including the insights such models provide into the cellular and molecular mechanisms of tauopathy, the direct relationship between neuropathology and behaviour, and the use of mouse models to help provide a platform for testing novel therapies. Mouse models have helped clarify the relationship between pathological forms of tau, cell death, and the emergence of disease, as well as the interaction between tau and other disease-associated molecules, such as the A beta peptide. Finally, we discuss potential future MAPT genomic DNA models to investigate the importance of alternative splicing of the MAPT locus and its role in sporadic tauopathies.