FIG 3.

Effect of intestinal epithelial cell-restricted Prnp ablation on prion accumulation in lymphoid tissues. Female Prnp^ΔIEC mice were treated with βNF for 5 days to specifically ablate Prnp expression in intestinal epithelial cells. Untreated Prnp^ΔIEC mice and Prnp^ΔIEC mice treated with the vehicle alone (Veh.) were used as controls. Fourteen days later, the mice were orally exposed to ME7 scrapie prions, and Peyer's patches, mesenteric lymph nodes (MLN), and spleens were collected at 70 days postinfection. (a) Immunohistochemical analysis reveals high levels of disease-specific PrP (PrP^d) (middle row, red, arrows) detected in association with FDC (CD21/35⁺ cells) (top row, red) in Peyer's patches from mice from each group. Sections were counterstained with hematoxylin to detect cell nuclei (blue). Analysis of adjacent sections by paraffin-embedded tissue immunoblotting confirmed the presence of prion-specific PK-resistant PrP^Sc (blue/black). Data are representative of results for tissues from 6 mice/group. (b to d) Prion infectivity levels were assayed in Peyer's patches (b), MLN (c), and spleens (d) from mice from each group collected at 70 days postinfection. Prion infectivity titers (log₁₀ i.c. ID₅₀ per gram of tissue) were determined by injection of tissue homogenates into groups of C57BL/Dk indicator mice (n = 4 recipient mice/tissue). Each symbol represents data derived from an individual tissue. Red line, median prion infectivity titer for groups in which all samples contained >1 log₁₀ i.c. ID₅₀/g tissue. Data below the broken horizontal line indicate disease incidence in the recipient mice of <100%, which were considered to contain trace levels of prion infectivity.