Regional distribution of PrP^Sc in the brains of Tg(BoPrP) mice inoculated with BSE prions. Sections A and B were from Tg(BoPrP)Prnp^0/0 mice inoculated with BSE prions, and sections C and D were taken from congenic B6.I-1 (Prnp^b/b) mice inoculated with 301V prions. A and C were through hippocampus and thalamus, and B and D were through the brainstem.

PrP residues governing the transmission of prions. NMR structure of recombinant SHaPrP (90–231) (57) shown with the putative epitope formed by residues 184, 186, 203, and 205 highlighted in red. Residue numbers correspond to SHaPrP. Additional residues (138, 139, 143, 145, 148, and 155) that might participate in controlling the transmission of prions across species are depicted in green. Residues 168, 172, 215, and 219 that form the epitope for the binding of protein X are shown in blue. The three helices (A, B, and C) are highlighted in brown. The illustration was generated with biosym/insight ii.

Western blots of PrP in brains from Tg mice inoculated with BSE prions and cattle with BSE. Each undigested control aliquot (− lanes) contained approximately 5 μg of total protein; aliquots digested with proteinase K (+ lanes) consisted of the equivalent of 25 μg of undigested, total protein. Samples in lane pairs: 1, bovine medulla from case PG31/90; 2, Tg(BoPrP)4092/Prnp^0/0, uninoculated; 3, Tg(BoPrP)4092/Prnp^0/0 clinically ill after inoculation with case PG31/90; 4, Tg(BoPrP)4092/Prnp^0/0 clinically ill after inoculation with case GJ248/85; 5, Tg(BoPrP)4125/Prnp^0/0, uninoculated; 6, Tg(BoPrP)4125/Prnp^0/0 clinically ill after inoculation with case PG31/90; 7, Tg(BoPrP)4125/Prnp^0/0 clinically ill after inoculation with case GJ248/85; 8, Tg(BoPrP)333 clinically ill after inoculation with PG31/90 prions; 9, Tg(BoPrP)333 clinically ill at approximately 500 days after inoculation with the sheep scrapie SSBP/1 isolate.

Neuropathology of Tg(BoPrP)Prnp^0/0 mice inoculated with BSE prions. (A) No pathological changes were found in the periaqueductal grey of the midbrain. (B) Mild to moderate vacuolar degeneration was found in the reticular formation of the midbrain tegmentum. (C) Reactive astrocytic gliosis colocalized with sites of vacuolar degeneration: astrogliosis in the red nucleus is shown here. (D) Little or no vacuolar degeneration was found in the tract or the nucleus of the spinal tract of the trigeminal nerve in the medulla. (E) Moderate to severe vacuolar degeneration occurred in the medial tegmentum of the medullary reticular formation. (F) Small PrP-immunopositive primitive plaque-like deposits colocalized with sites of the most severe vacuolar degeneration. Diagrams show locations of photomicrographs. Hematoxylin and eosin stain was used in A, B, D, and E. Glial fibrillary acidic protein immunohistochemistry was used in C. PrP immunohistochemistry was used in F. Bar in E = 100 μm and also applies to A, B, and D. Bar in F = 50 μm and also applies to C. Italicized letters identify selected brainstem structures: CP, cerebral peduncle; IP, interpeduncular nucleus; PG, periaqueductal grey; Py, pyramidal tract; RN, red nucleus; Sol, nucleus and tractus solitarius; Sp5, nucleus of the spinal tract of the trigeminal nerve.