Follicular Dendritic Cell-Specific Prion Protein (PrPc) Expression Alone Is Sufficient to Sustain Prion Infection in the Spleen
Figure 5
FDC-restricted PrPc-ablation in the spleens of Prnpflox/-→CD21-Cre Prnpflox/- mice.
A) The anticipated distribution of PrPC expression on FDC and B cells in tissues from each mouse group. B) PCR analysis of DNA isolated from the spleens, blood and tails of Prnpflox/-→CD21-Cre Prnpflox/- mice confirmed that efficient Cre-mediated DNA recombination and Prnp-ablation (Prnpdeflox) was restricted to the FDC-containing stromal compartment of the spleen. Cre-mediated recombination of CD21-expressing lymphocytes was efficiently prevented in these mice by the irradiation and transfer of Prnpflox/- bone marrow as demonstrated by the lack of a Prnpdeflox band in DNA extracted from blood (lower panel). B, blood; S, spleen; T, tail; M, DNA size markers; a, b, c, d control DNA samples for each transgene combination tested which were (a) Prnpflox/flox,(b) Prnpflox/-, (c) Prnp-/- and (d) Prnpflox/- with complete recombination of the floxed exon 3. C) IHC analysis of PrPC expression (blue) by FDC (CD35+ cells; red) and sympathetic nerves (TH+ cells, green) confirmed the PrPC-ablation was restricted to FDC in spleens of Prnpflox/-→CD21-Cre Prnpflox/- mice. Scale bar, 100 µm. D) Morphometric analysis confirmed that the magnitude of the PrPC expression co-localized upon the surfaces of FDC in the spleens of Prnpflox/-→CD21-Cre Prnpflox/- mice was significantly lower than that observed upon FDC from Prnp+/-→Prnp+/- control mice (P<1.0×10-24, n = 48 FDC networks/group). In contrast, in the absence of Cre-recombinase expression by FDC in CD21-Cre Prnpflox/-→Prnpflox/-mice, PrPC expression was similar to that observed upon FDC in spleens from Prnp+/-→Prnp+/- control mice (P = 0.106, n = 48 FDC networks/group). E) Morphometric analysis confirmed that the magnitude of the PrPC expression co-localized upon the surfaces sympathetic nerves in the spleens of Prnpflox/-→CD21-Cre Prnpflox/-, CD21-Cre Prnpflox/-→ CD21-Cre Prnpflox/- and CD21-Cre Prnpflox/-→Prnpflox/- mice was not significantly different when compared to that observed upon sympathetic nerves in spleens from Prnp+/-→Prnp+/- control mice (p = 0.400, n = 48 sympathetic nerves/group). For all panels n = 6 mice/group.