Figure 3: Repeat time course of RML prion infection in FVB/N wild-type mice used for detailed neuropathological analysis.
FVB/N mice were infected with RML prions and the mean incubation period for these mice was (in days±s.d.) 168±2.5. Mice were culled at defined time points or at onset of disease and prion titres were determined using scrapie cell assay (SCA) or scrapie cell assay in end-point format (SCEPA) for low-titre samples. Prion titres (log tissue-culture infectious units per gram brain; bars indicate s.e.m. and, in some cases, are smaller than the symbols used to designate mean) are closely similar to those described previously3 (closed circles; dotted lines). Normal interval regression was used to calculate mean and s.e.m for timed culls where one or more samples were below assay sensitivity cut-off. This only applied to samples up to day 30 of the time course. All samples from two timed culls in the infectivity time course (5 and 15 days) were below assay sensitivity cut-off and therefore are not shown. Total PrP comprising PrPC, classical PK-resistant PrP (PrPSc) and disease-related but PK-sensitive PrP isoforms were determined using ELISA (closed circles; solid lines). In addition, PrPSc was quantified after PK digestion by ELISA (open circles; solid lines). Total PrP and PrPSc levels are presented relative to a clinical end-point reference; bars indicate s.e.m and, in some cases, are smaller than symbol used to designate mean; group sizes were four to six.
