Altering the flexible loop that connects the β-2 strand and α2 helix of mouse PrP to the rigid loop found in cervid PrPC via amino acid substitutions S170N and N174T resulted in spontaneous prion disease in vivo (22), while changing the rigid loop structure from a 310- to a type I β-helix turn by introducing a Y169G mutation prevented prion disease (34). Here, PRNP is linked to prion disease.