Unaltered susceptibility to BSE in transgenic mice expressing human prion protein

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Abstract
PRION diseases are transmissible neurodegenerative conditions of humans and animals. Prions consist principally of a post-translationally modified form of prion protein (PrP), PrPSc, which is partly protease resistant1. Transmission of prion diseases between species is limited by a 'species barrier'2 determined in part by the degree of sequence homology between host PrP and inoculated prpSc (ref. 3) and by prion strain type4. The epidemic of bovine spongiform encephalopathy (BSE) in the United Kingdom and other countries has led to concerns that transmission to humans may occur by dietary exposure. BSE appears to be caused by a single strain, distinct from those of natural or experimental scrapie4, which is also seen in the new prion diseases of cats and ruminants that have presumably arisen from dietary BSE exposure4. Here we show that transgenic mice expressing human PrP in addition to mouse PrP can generate human PrPSc and 'human' prions. These mice therefore provide a model to study experimentally the species barrier limiting BSE transmission to humans. Incubation periods to BSE in transgenic mice are not shortened by expression of human PrP, and only mouse PrPSc is produced in response to such challenge.