Transgenic mouse models of prion diseases

Prions represent a new biological paradigm of protein-mediated information transfer. In mammals, prions are the cause of fatal, transmissible neurodegenerative diseases, often referred to as transmissible spongiform encephalopathies. Many unresolved issues remain, including the exact molecular nature of the prion, the detailed mechanism of prion propagation, and the mechanism by which prion diseases can be both genetic and infectious. In addition, we know little about the mechanism by which neurons degenerate during prion diseases. Tied to this, the physiological function of the normal form of the prion protein remains unclear, and it is uncertain whether loss of this function contributes to prion pathogenesis. The factors governing the transmission of prions between species remain unclear, in particular the means by which prion strains and PrP primary structure interact to affect interspecies prion transmission. Despite all these unknowns, dramatic advances in our understanding of prions have occurred because of their transmissibility to experimental animals and the development of transgenic mouse models has done much to further our understanding about various aspects of prion biology. In this chapter, I review recent advances in our understanding of prion biology that derive from this powerful and informative approach.