Fig. 7

Rats overexpressing rat PrP show accelerated prion disease onset. (a) The rat Prnp ORF was restored in the RaPrnp vector by In-Fusion cloning. Schematic of the RaPrnp-PrP construct used to generate founder rat lines. (b and c) Comparing PrP expression level (y-axis, relative to WT PrP expression) to copy number (x-axis) in Tg(RaPrnp-PrP) founder rats. Graph in (b) compares all Tg(RaPrnp-PrP) founders, while the dashed boxed area is magnified to show the relationship between PrP expression and ≤10 copies of the RaPrnp-PrP transgene (c). Tg2922 and Tg2919 are indicated by red circles in (b) and (c), respectively. (d) Western blot showing rat PrP expression in multiple tissues from 4-month-old WT, Tg2919, and Tg2922 rats. (e) Kaplan–Meier plot demonstrates accelerated disease progression in rat RML-inoculated Tg2919 and Tg2922 rats compared with WT controls. (f) PK digestion studies of PrP in NBH or rat RML inoculated WT rats. (g and h) PK digestion studies of PrP in age-matched controls to Tg2919 and Tg2922 rats inoculated with rat RML. All western blotting experiments were done with an Anti-P antibody. Molecular weight is given in kilodaltons (kDa)