E/D163 polymorphism of dog
prion protein (PrP) has been recently proposed as the variant responsible for canid
prion resistance. To further investigate the protective role of this variant against
prion replication, the transgenic mouse model OvPrP-Tg532 expressing sheep/goat PrP carrying the substitution D162 (equivalent to D163 position of dog PrP) was generated and intracranially inoculated with a broad collection of small ruminant
prion strains. OvPrP-Tg532 mice showed resistance to classical
bovine spongiform encephalopathy (BSE) from sheep and some classical
scrapie isolates from sheep and goat but were susceptible to ovine atypical L-BSE and numerous classical
scrapie isolates. Strikingly, some of these classical
scrapie isolates showed a shift in their
prion strain properties. These results suggest that other PrP residues apart from E/D163 variant of dog PrP or factors distinct than PrP may participate in
prion resistance of canids and that different factors may be required for D162 sheep PrP to provide effective protection to sheep against ruminant
prions.