FIGURE 3.

Neuron‐selective, but not astrocyte‐selective, PrP^C expression confers susceptibility to prion disease. (A) Survival of Syn^Cre;loxPrP, loxPrP, Syn^Cre, Prnp ^ZH3/ZH3 and wild‐type mice inoculated intracerebrally with RML6 prions. The median incubations for Syn^Cre−;loxPrP (n = 5) and wild‐type mice (n = 4) were 435 and 195 days post inoculation (dpi), respectively. Survival curves were compared by a log‐rank (Mantel‐Cox) test. (B) Total PrP (upper panel) and PK‐resistant PrP^Sc (lower panel) in brains of prion‐infected, terminally sick mice. Syn^Cre;loxPrP and wild‐type brains, but not loxPrP brains, contained PrP^Sc. β‐actin: loading control. Lane #2 (upper panel) was intentionally underloaded to avoid overexposure. (C) Survival curves of GFAP1^Cre;loxPrP, loxPrP, Prnp ^ZH3/ZH3 and wild‐type mice inoculated with RML6 prions intracerebrally. GFAP^Cre;loxPrP (n = 5) did not develop clinical signs of prion disease. Wild‐type mice (n = 4): 167 dpi (median incubation time). One of the GFAP^Cre mice was sacrificed (544 dpi) because of acute dermatitis and did not exhibit scrapie signs or PrP^Sc accumulation. (D) Western blot of total PrP and PK‐digested PrP^Sc in brain homogenates of prion‐infected GFAP^Cre;loxPrP (627 dpi) and control mice. GFAP^Cre;loxPrP harbor copious PrP^Sc. (E) Hippocampal and cerebellar histology of prion‐infected Syn^Cre;loxPrP, GFAP^Cre;loxPrP, loxPrP, and Prnp ^+/+ mice. Slices were stained with hematoxylin and eosin (H&E) and anti‐PrP antibody SAF84. Both astrocyte‐ and neuron‐restricted PrP transgenic mice accumulated PrP^Sc, but their deposition patterns differed profoundly. Blue arrows in cerebellar regions of Syn^Cre;loxPrP and GFAP^cre;loxPrP: PrP^Sc deposits