PRNP and prion disease: In strong and independent support of a central role for altered PrP in disease pathogenesis and replication of the transmissible agent, missense mutations in the murine prion protein structural gene, Prnp, that create the allelic forms Prnpa and Prnpb cause a modulation of prion disease phenotypes and differential susceptibility to prion strain isolates [3]–[5], while knockout of mouse Prnp renders animals completely resistant to experimental prion infections [6].