Both host prion protein 131-188 subregion and prion strain characteristics regulate glycoform of PrP Sc.
Prion proteins (PrPs) contain 2 N-linked glycosylation sites and are present in cells in 3 different forms. An abnormal isoform of prion protein (PrP(Sc)) has different glycoform patterns for different prion strains. However, the molecular basis of the strain-specific glycoform variability in prions has remained elusive. To understand the molecular basis of these glycoform differences, we analyzed PrP(Sc) in 2 lines of transgenic mice (MHM2 and MH2M with PrP null background) that expressed a chimeric PrP. Our result indicated that PrP 131-188 (substitutions at I139M, Y155N, and S170N) contributed to both PrP(C) and PrP(Sc) glycoform ratios. Furthermore, the PrP(Sc) glycoform pattern within these transgenic mice showed a subtle difference depending on the inoculated prion. This study indicated that the PrP(Sc) glycoform ratio was influenced by both host PrP(C) and the prion strain.