The study investigates the role of amino-terminal deletions in the susceptibility of PrP knockout mice to scrapie. The authors introduced transgenes encoding wild-type PrP or PrP lacking 26 or 49 amino-terminal residues into PrP knockout mice. Inoculation with prions led to fatal disease, prion propagation, and accumulation of PrPSc in mice expressing both wild-type and truncated PrPs. This suggests that the amino-terminal segment of PrPC is not required for its susceptibility to conversion into the pathogenic, infectious form of PrP or for the generation of PrPSc. The findings support the 'protein only' hypothesis, which posits that the prion is a modified form of the host protein PrPC and that it multiplies by converting the normal form into a similar form.The study investigates the role of amino-terminal deletions in the susceptibility of PrP knockout mice to scrapie. The authors introduced transgenes encoding wild-type PrP or PrP lacking 26 or 49 amino-terminal residues into PrP knockout mice. Inoculation with prions led to fatal disease, prion propagation, and accumulation of PrPSc in mice expressing both wild-type and truncated PrPs. This suggests that the amino-terminal segment of PrPC is not required for its susceptibility to conversion into the pathogenic, infectious form of PrP or for the generation of PrPSc. The findings support the 'protein only' hypothesis, which posits that the prion is a modified form of the host protein PrPC and that it multiplies by converting the normal form into a similar form.