We and others have shown that mice devoid of PrPC (Prnp0/0) are resistant to prions, neither developing disease nor propagating PrPSc or prions in their brains after intracerebral inoculation with the prions (6, –, 9), indicating that the conversion of PrPC into PrPSc is a key pathogenic event in prion diseases. Here, PRNP is linked to prion disease.