Figure 1: Levels of total PrP and PrPSc in the brain during prion infection.

Three different lines of FVB/N mice: Prnp+/0 with 50% wild-type PrPC expression (i); Prnp+/+ with wild-type PrPC expression (ii); and Tg20 with ~eightfold overexpression of PrPC (iii) were intracerebrally infected with RML prions. Mean incubation periods are indicated by arrows and were (in days±s.d.): Prnp+/0, 258±23.5; Prnp+/+, 137±1.5; and Tg20, 59.5±2.0. Mice were culled at defined time points or at clinical onset of disease. 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 as described previously3 (closed circles; dotted lines). Total PrP comprising PrPC, classical PK-resistant PrP (PrPSc) and disease-related but PK-sensitive PrP isoforms were determined by 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 as a ratio relative to a clinical end point reference; bars indicate s.e.m and, in some cases, are smaller than the symbol used to designate mean; group sizes were three to six.