Figure 1. Atypical BSE transmission into human-PrP transgenic mice before and after adaptation to sheep PrP sequence in a study of atypical BSE transmission using isolates from different countries in Europe and transgenic mouse models overexpressing human normal brain prion protein. A) Transmission data including mean survival time + SD as well as attack rates (diseased PrP^res positive/inoculated animals) and PET blot images for all atypical BSE transmission into the human-PrP transgenic mouse models. L-BSE/TgMet₁₂₉ showed fine staining, and deposits were restricted to the several thalamus nuclei. C-BSE/TgMet129 showed granular deposits. L-BSE/TgVRQ/TgVal₁₂₉ and TgVal₁₂₉ PET blotting showed strong deposition in a particular area of the isocortex, thalamus, and midbrain, and mild deposition in the fiber tracts. H-BSE/TgVRQ and sCJD MM1 PET blotting images showed strong deposition in the isocortex area, hippocampus, thalamus, and midbrain in TgMet₁₂₉ and strong deposition in the isocortex area, thalamus, and midbrain in TgVal₁₂₉. B) Brain PrP^res profile in TgMet₁₂₉ and TgVal₁₂₉ mice inoculated with atypical BSE prions before or after adaptation to the sheep-PrP sequence immunoblotted with the Sha31 mAb. Human vCJD and different sCJD prion strains inoculated in the same TgMet₁₂₉ and TgVal₁₂₉ mouse models are also included for comparison purposes. L-BSE/TgVRQ/TgVal₁₂₉ (lane 3) is very similar to sCJD VV2/TgVal₁₂₉ (lane 9). By contrast, H-BSE/TgVRQ/TgMet₁₂₉ (lane 5) and sCJD MM1/TgMet₁₂₉ (lane 6) are undistinguishable, as also observed with H-BSE/TgVRQ/TgVal₁₂₉ (lane 4) and sCJD MM1/TgVal₁₂₉ (lane 7). All PrP^res profiles are different from those of vCJD/TgMet₁₂₉ (lanes 1 and 10) and L-BSE/TgMet₁₂₉ (lane 2). All inoculated animals were analyzed, and individual variations in the PrP^res profile among them were not found. C) Vacuolar lesion profile in brains from human-PrP transgenic mice inoculated with C-BSE or the atypical BSE isolates before and after adaptation to the sheep-PrP sequence. Lesion scoring was conducted for 9 areas of gray matter (G) and 3 areas of white matter (W) in mouse brains: G1, dorsal medulla; G2, cerebellar cortex; G3, superior colliculus; G4, hypothalamus; G5, medial thalamus; G6, hippocampus; G7, septum; G8, medial cerebral cortex at the level of the thalamus; G9, medial cerebral cortex at the level of the septum (G9); W1, cerebellum; W2, mesencephalic tegmentum; W3, pyramidal tract. BSE, bovine spongiform encephalopathy; C-BSE, classical bovine spongiform encephalopathy; mAb, monoclonal antibody; PET, paraffin embedded tissue; PrP, prion protein; PrPres, proteinase K–resistant prion protein; sCJD, sporadic Creutzfeldt-Jakob disease; vCJD, variant Creutzfeldt-Jakob disease.