To estimate the molecular component of transmission barriers for particular TSE agents between species, we used PMCA reactions to amplify PrPd associated with vCJD (10), bovine BSE (11), ovine scrapie (12), and experimental ovine BSE (13) and substrates prepared from humanized transgenic mouse brain tissue expressing each of the 3 main PRNP polymorphic variants found in Caucasian human populations (PRNP-129MM, MV, and VV) (14). The gene discussed is PRNP; the disease is scrapie.