The pattern of scrapie prion protein (PrPSc) accumulation in the brain
is different for each prion strain. We tested whether the PrPSc depos
ition pattern is influenced by the Asn-linked oligosaccharides of PrPC
in transgenic mice. Deletion of the first oligosaccharide altered PrP
C trafficking and prevented infection with two prion strains. Deletion
of the second did not alter PrPC trafficking, permitted infection wit
h one prion strain, and had a profound effect on the PrPSc deposition
pattern. Our data raise the possibility that glycosylation can modify
the conformation of PrPC. Glycosylation could affect the affinity of P
rPC for a particular conformer of PrPSc, thereby determining the rate
of nascent PrPSc formation and the specific patterns of PrPSc depositi
on.