Modeling of p-dCJD and traceback phenomenon. (a) Schematic diagram of the modeling study. The 129 V/V mice were highly susceptible to the 129 M/M mouse-passaged sCJD-VV2, i.e., Mi PrPSc, despite their incompatible codon 129 genotypes. Moreover, the altered neuropathological and biochemical phenotypes in the primary passage in the 129 M/M mice reverted to the original ones in the secondary passage in the 129 V/V mice. This is because the origin of Mi PrPSc is V2 PrPSc. This phenomenon has been designated as traceback [20, 26]. (b) Immunohistochemical analysis of PrPSc in the brains from the PrP-humanized mice infected with the 129 M/M mouse-passaged sCJD-VV2. G, gray matter; W, white matter. (c) Westernblot analysis of PrPSc in the brains from the PrP-humanized mice infected with sCJD-VV2 or the 129 M/M mouse-passaged sCJD-VV2. 129 M/M, knock-in mice expressing human PrP with the 129 M/M genotype; 129 V/V, knock-in mice expressing human PrP with the 129 V/V genotype.