Transgenic Mice Modelling

Although the prion protein (PrP) was discovered in the early 1980s, there is still a considerable lack of knowledge of the normal function of the PrP protein and its precise role in the infectious process of transmissible spongiform encephalopathies (TSEs) or prion diseases. The production and use of a multitude of transgenic mice expressing different forms of PrP has enabled us to increase our knowledge of PrP in health and disease. Using mice expressing PrP from different species, we are able to define the strain of TSE agent infecting a wide range of hosts and model the transmission potential of each agent within and between species. Transgenic mouse models are also utilised in investigating the normal function of PrP, the impact of differential glycosylation in PrP biology and the genetics underlying disease susceptibility. Advances in transgenic technologies have enabled us to control both spatial and temporal expression of PrP, allowing us to define the mechanisms and routes of disease pathogenesis. Transgenic mice also play a vital role in understanding the mechanisms of neurodegeneration in the TSEs, which may also lead to a better understanding of the other protein misfolding diseases such as Alzheimer’s disease.