Fas Stabilizes and Accelerates Erythropoiesis Figure 6. Delayed response to Epo-induced stress in mice deficient in the Fas pathway. (A–D) gld-Rag12/2, lpr-Rag12/2 and matched Rag12/2 control mice were injected with Epo (300 U/ 25 g body weight) subcutaneously at t = 0. The erythropoietic response was followed for 6 days. Data is mean 6 sem for 3 to 18 mice per time point per genotype, pooled from up to 3 experiments per time point. Data at t = 0 is the basal state data shown in Figures 3A and 5A, pooled for males and females. (A) Hematocrit measurements (B) Spleen EryA (cells per gram body weight) in the same mouse set as in the top panel. Data points are individual mice, with the mean 6sem for each day marked as a horizontal line. (D) The difference in mean EryA number (shown in panel B) between the mutant gld-Rag12/2 or lpr-Rag12/2 and their matched Rag12/2 controls, for each day. The size of the corresponding control (Rag12/2) EryA pool is marked with a black bar. For all panels: *p,0.05, **p,0.005, ***p,0.0005 (t test, unequal variance). (D) The rate of change in hematocrit between days 2 and 3 following Epo injection. The same dataset as in panel (A), showing the differences in hematocrit measured in multiple independent experiments on days 2 and 3. Altogether 5 independent comparisons are shown. For all panels: *p,0.05, **p,0.005, ***p,0.0005 (t test, unequal variance). doi:10.1371/journal.pone.0021192.g006 own survival via the Fas/FasL interaction, accounts well for the experimental data correlating splenic EryA frequency with their Fas expression, across a wide range of Epo concentrations in vivo (Fig 2 and Text S2). Fas-mediated negative autoregulation decreases erythropoiesis at the whole-animal level Both acute and chronic inhibition of Fas suggest that it negatively regulates erythropoiesis at the level of the whole PLoS ONE | www.plosone.org 9 July 2011 | Volume 6 | Issue 7 | e21192