In this study, to investigate the role of the octapeptide repeat (OR) region alone in the N-terminal domain for the susceptibility and pathogenesis of prion disease, we intracerebrally inoculated RML scrapie prions into tg(PrPΔOR)/Prnp0/0 mice, which express mouse PrP missing only the OR region on the PrP-null background. This evidence concerns the gene PRNP and scrapie.