Dr Majid Hafezparast and Dr Timothy Chevassut, University of Sussex
Development of induced pluripotent stem (iPS) cells from mutant mouse models in order to reduce animal use
Abstract of research
Cytoplasmic dynein is a large protein involved in a range of cellular processes including transport of intracellular material and cell division. Mice with mutations in the gene encoding this protein show defective motor and sensory functions. Because of their wide range of functions and implications for neuronal survival, these proteins are being widely studied around the world using the mouse as a model organism.
Mouse models are used to elucidate the mechanisms that regulate the motor and cargo transport functions of dynein, and its role in neuronal health and disease. However, large numbers of mice and lengthy breeding programmes are needed to obtain the required motor and sensory primary neurones for such analyses. In addition, the neurones isolated are not able to proliferate and die within 2-3 weeks in culture, necessitating the continuous breeding of large numbers of mice.
In this project, induced pluripotent stem cells (iPS) will be produced from mouse embryonic fibroblasts taken from animals with mutations of interest. IPS cells have the potential to turn into any cell type, so they can be differentiated into neuronal cells for use in this area of research. Currently, 4000 mice are used in one laboratory per year for this purpose and, if successful, this work will use 660 mice but result in an unlimited supply of cells. So the result will be a significant reduction in breeding mice with harmful mutations in dynein. In addition, the supply of cells can be shared with other laboratories around the world, and will demonstrate the potential of this approach to reduce the use of mice in the study of other mouse models.
