Figure 2.

Prnp-siRNA treated and PrP-deficient (PrP^−/−) mice develop more severe EAE whereas mice overexpressing PrP^C are protected. (A and B) In vivo silencing of PrP^c worsens the clinical course of actively induced EAE in SJL/J mice. (A) In an EAE ‘prevention’ experiment, SJL/L mice were injected intravenously with a single dose of Prnp-siRNA or nonsense (NS)-siRNA at the time of immunization with PLP_p139−151, as indicated by a grey arrow. Prnp-siRNA treatment resulted in clinically more severe disease. (B) In an EAE ‘treatment’ experiment, Prnp-siRNA or nonsense-siRNA was injected at the time of clinical onset of EAE (grey arrow). Mice treated with Prnp-siRNA had a significantly worse initial clinical exacerbation. (C) Male and (D) female PrP^−/− mice had earlier disease onset and significantly higher disease scores than male wild-type (WT) mice. (E) Tga20 mice had a delayed disease onset, and developed only mild EAE compared to C57BL/6 and Sv129 wild-type mice.