New viral-mediated TDP-43 mouse models of MND

Mouse models are important for pre-clinical testing of potential new drugs for MND, but the mouse models that are currently available do not completely recapitulate the human disease pathology and phenotype and are slow and difficult to generate. In preliminary studies, we have used new viral vector technology to develop new mouse models of MND that show disease-reminiscent pathology and signs of motor function decline. These viral-mediated models are faster and simpler to generate for laboratories than traditional approaches. The aim of the current project is to fully characterise and test a suite of these new MND mouse models, to provide baseline data demonstrating their utility for use in mechanistic studies to understand disease causes, and for preclinical testing. We will generate mice with MND-like pathology in the brain and/or the spinal cord, and characterise the biochemistry and pathological changes in the central nervous system and muscles, with longitudinal analysis of disease signs measured using a series of behavioural tests. This work will provide the broader MND research community with a resource to increase the speed of testing of potential new drugs in mouse