In 1991 Victor Tybulewicz (at MRC NIMR) and I gained funding from the Wellcome Trust to start a long-term project to create a new ‘humanised’ mouse model of Down syndrome, which led to the research project we now pursue jointly to use mouse molecular genetics to find the individual dosage sensitive genes giving rise to aspects of Down syndrome. In parallel my lab has also created and analysed a series of mouse models with motor neuron degeneration, trying to shed light on why motor neurons die in the disease amyotrophic lateral sclerosis. These two research themes come together in an interest in mouse models in neurodegeneration.