Transgenic Models for Prion Disease: Have They Outlived Their Useful Purpose?

Abstract

Prions are a recently identified class of proteinaceous pathological agents. Prion diseases are fatal neurological disorders, the importance of which is exemplified by the recent emergence of a novel variant of Creutzfeldt-Jacob disease (CJD) in humans. During pathogenesis, prion proteins undergo a conformational change, which converts the normal isoform to a pathogenic isoform. Several approaches are available for studying prion disease. The predominant approach has involved in vivo studies, especially involving transgenic mice. In vitro alternatives available for studying prion disease include a cell-free conversion assay, cell culture systems, and an immunoassay for the pathogenic form of the prion protein. Prion-like proteins have been identified in yeast, and therefore this constitutes another non-animal approach. Four main areas of prion research are discussed in this paper, to illustrate the potential applications and limitations of the in vivo and alternative systems. From this study, we conclude that, while current in vitro approaches can be used initially, in vivo studies are still needed to confirm data obtained in vitro. Priority should be given to the non-animal alternatives, as well as to developing new methods, and these should be given primary consideration at the outset of a project.