Microglia-deficient IL34−/− mice demonstrated accelerated prion pathogenesis. (A) qRT-PCR for Prnp mRNA in one hemisphere of IL34−/− and IL34+/+ brains. n = 4. n.s, P > 0.05. (B) PrPC Western blot for one hemisphere from IL34−/− and IL34+/+ brains. n = 4. (C) Survival curves of RML6 infected IL34−/− and IL34+/+ (WT) mice. Median survival of IL34−/− females 162 dpi (n = 17) versus IL34+/+ (WT) females 176 dpi (n = 17). **, P < 0.01; median survival of IL34−/− males 170 dpi (n = 8) versus IL34+/+ (WT) males 191 dpi (n = 15). ****, P < 0.0001. (D and E) Hematoxylin and eosin and SAF84 staining on RML6-infected IL34−/− and IL34+/+ (WT) brains at 105 dpi (D) and 150 dpi (E). Bars, 50 µm. (F and G, left) PrPSc Western blot of homogenates prepared from one brain hemisphere of RML6-infected IL34−/− and IL34+/+ (WT) mice at 105 dpi (F) and 150 dpi (G). Samples were digested with PK as indicated and detected with POM1. (right) Densitometric quantification of the PrPSc Western blot. n = 4 (105 dpi) or 5 (150 dpi) for IL34−/−; n = 4 (105 dpi) or 6 (150 dpi) for IL34+/+. **, P < 0.01; *, P < 0.05. Error bars represent SEM. Survival curves summarize two independent i.c inoculation experiments. Statistical significance in A, F, and G was determined using unpaired Student’s t test. Statistical significance in C and D was determined using Log-rank (Mantel-Cox) test. qRT-PCR, histology, and Western blot results represent at least four independent experiments.
