(A) Western blots reveal 22L- and ME7-infected Prnp180Q/196Q mice harbor higher levels of ADAM10-cleaved PrPSc in the brain compared with WT mice; n = 3/group. Note that the PK-digested ADAM10-cleaved PrP runs at a lower molecular weight due to lack of the GPI-anchor and terminal 3 amino acids. *P ≤ 0.05, unpaired, 2-tailed Student’s t test. (B) Western blots show that uninfected Prnp180Q/196Q and WT mice have similar levels of ADAM10-cleaved/total PrPC in the brain; n = 5 WT and 11 Prnp180Q/196Q mice. (C) Brain sections immunolabeled for PrP with SAF84 (labelled PrP) or with sPrPG228 antibody (labelled ADAM10-cleaved PrP) reveal ADAM10-cleaved PrP localizes to plaque-like and plaque deposits in ME7-infected Prnp180Q/196Q, mCWD-infected Prnp180Q/196Q, and WT brain sections. Note that the diffuse aggregates are not labelled by the sPrPG228 antibody. Cortex (ME7-infected WT), thalamus (ME7-infected Prnp180Q/196Q), hippocampus (mCWD-infected Prnp180Q/196Q), and corpus callosum (WT-infected mCWD) are shown. Scale bar: 50 μm.