Abstract
Prion strains occur in natural prion diseases, including prion diseases of humans. Prion strains can correspond with differences in the clinical signs and symptoms of disease and the distribution of prion infectivity in the host and are hypothesized to be encoded by strain-specific differences in the conformation of the disease-specific isoform of the host-encoded prion protein, PrPTSE. Prion strains can differ in biochemical properties of PrPTSE that can include the relative sensitivity to digestion with proteinase K and conformational stability in denaturants. These strain-specific biochemical properties of field isolates are maintained upon transmission to experimental animal models of prion disease. Experimental human models of prion disease include traditional and gene-targeted mice that express endogenous PrPC. Transgenic mice that express different polymorphs of human PrPC or mutations in human PrPC that correspond with familial forms of human prion disease have been generated that can recapitulate the clinical, pathologic, and biochemical features of disease. These models aid in understanding disease pathogenesis, evaluating zoonotic potential of animal prion diseases, and assessing human-to-human transmission of disease. Models of sporadic or familial forms of disease offer an opportunity to define mechanisms of disease, identify key neurodegenerative pathways, and assess therapeutic interventions.