Julianna L. Sun, Sehun Kim, Jenna Crowell, Bailey K. Webster, Emma K. Raisley, Diana C. Lowe, Jifeng Bian, Sirkka-Liisa Korpenfelt, Sylvie L. Benestad, and Glenn C. Telling
Figure 6. Responses of Finland, Norway, and North America moose chronic wasting disease (CWD) prions propagated in CWD-susceptible mice to increasing concentrations of GdnHCl. A) Responses of CerPrPSc in central nervous system (CNS) of diseased GtQ mice to proteinase K treatment after denaturation with increasing concentrations of GdnHCl. Magenta symbols indicate M-F1 CWD, green symbols M-NO1 CWD, and blue symbols M-US1 CWD. B) Denaturation profiles of cervid PrP scrapie in CNS of GtQ mice infected with M-F1. Magenta squares and solid lines depict passage 1; dotted magenta squares and dashed lines depict GtQ (M-F1) brains 1 and 2 (passage 2). C) Denaturation profiles of cervid PrP scrapie in the CNS of TgQ mice infected with M-F1 (magenta circles), TgQ mice infected with M-F1 passaged through TgE mice [TgE (M-F1)] (orange circles), and TgQ mice infected with M-F1 passaged through TgQ mice [TgQ (M-F1)] (dotted magenta circles). Proteinase K–resistant PrPSc was quantified by densitometry of immunoprobed dot blots and plotted against GdnHCl concentration. Sigmoidal dose-response curves were plotted using a 4-parameter algorithm and nonlinear least-square fit. Error bars indicate +SEM of data from analyses of >3 animals per group. GdnHCl1/2 values (mol/L) for each infection are reported on the right-hand side of each graph. Significance calculated by pairwise analysis of GdnHCl1/2 values from best fit curves. Fapp, fraction of apparent PrPSc = (maximum signal-individual signal)/(maximum signal-minimum signal); GdnHCl, guanidine hydrochloride; GdnHCl1/2, guanidine hydrochloride half-maximal denaturation; GtQ, CWD-susceptible gene-targeted mice in which the prion protein coding sequence was replaced with one encoding glutamine at codon 226; NS, not significant; PK, proteinase K; PrP, prion protein; TgE, transgenic mice expressing cervid PrP with glutamate at residue 226; TgQ, transgenic mice expressing cervid PrP with glutamine at residue 226.