MICE DEVOID OF PRP ARE RESISTANT TO SCRAPIE

S. B. Prusiner proposed that the infectious agent of scrapie, the prio n, is PrP(Sc), a modified form of the normal host protein PrP(C). Prn- p0/0 mice devoid of PrP(C) showed normal development and behavior. Whe n inoculated with mouse scrapie prions, they remained free of scrapie symptoms for at least 13 months while wild-type controls all died with in 6 months. Surprisingly, heterozygous Prn-p0/+ mice also showed enha nced resistance to scrapie. After introduction of Syrian hamster PrP t ransgenes, Prn-P0/0 mice became highly susceptible to hamster but not to mouse prions. These experiments show that PrP(C), possibly at close to normal levels, is required for the usual susceptibility to scrapie and that lack of homology between incoming prions and the host's PrP genes retards disease.