PRNP and scrapie: Intracerebral transmission of natural sheep scrapie isolates referred to as LAN isolates [9, 34] to multiple lines of transgenic mice expressing ovine PrPC (VRQ allele at codons 136, 154 and 171 of the PrP-encoding gene, where V, R, and Q stand for valine, arginine, and glutamine, respectively) at variable levels revealed that PrPC expression levels in the brain critically determine prion substrain selection [29].