Figure 1.
Neural grafts overexpressing PrPC in a Prnp-deficient host. (a) Schematic drawing of the transplantation procedure. (b–d) Coronal section of the thalamus of a PrP-overexpressing tg20 mouse 78 days after inoculation into the right eye. At time of analysis, the animal showed clinical symptoms of scrapie. (b) Pronounced gliosis in the visual pathway (optic tract and lateral geniculate nucleus, LGN) is visualized by immunocytochemistry for glial fibrillary acid protein (GFAP). (c and d) Asymmetric neurodegeneration of the LGN is visualized by synaptophysin immunostain. The affected left LGN displays coarse granular deposits and patchy staining that reflects significant synaptic loss, whereas the unaffected right LGN displays the fine granular synaptic stain typical of normal neural tissue. Because scrapie infection starts in the visual system and is followed by generalized disease in the CNS, the LGN and superior colliculus show a more prominent astrocytic reaction and severe loss of neuronal processes than other regions of the brain, e.g., the hippocampus. (e, g, and i) Graft (gr) and adjacent host brain (h) in hematoxylin and eosin stains. (f, h, and k) Immunohistochemical stain for GFAP. (e and f) Neural graft (tg20) in a Prnpo/o host brain analyzed 232 days after grafting without scrapie inoculation. Cellular density and distribution of neurons and astrocytes within the graft are similar to that of normal host brain. The slightly enhanced GFAP stain results from the transplantation procedure. (g and h) Neural graft (tg20) in a Prnpo/o host brain analyzed 231 days after grafting and 230 days after direct intracerebral infection with mouse prions. Spongiosis (g) and gliosis (h) are conspicuous within the graft and were not observed in uninoculated or mock-inoculated grafts (not shown). (i and k) Neural grafts (tg20) 217 days after transplantation in a Prnpo/o host brain and 305 days after intraocular inoculation show no neuropathological changes. The asterisks label the border between graft and host tissue.