Fig. 7: Delayed onset of APLAID phenotype in G-CSF-deficient mice.
a, Schematic of BM chimera generation. Plcg2S707Y/+ (yellow) is the donor for lethally irradiated WT (blue) or G-CSF−/− recipients (green). Single-cell suspension of BM cells (1 × 106/ml) were transplanted by i.v. injection into recipient animals 3 h after irradiation. b, APLAID skin score revealed an autoinflammatory phenotype in WT mice receiving a Plcg2S707Y/+ transplant at day 18, while G-CSF knockouts showed a beginning weight loss at day 70. c, Growth curve exhibiting dramatic weight loss in WT mice following irradiation and reconstitution with Plcg2S707Y/+ BM cells. d, Kaplan–Meier survival curve showing prolonged survival rates of 52 d in G-CSF−/− mice receiving Plcg2S707Y/+ BM cells. e, Quantification of plasma G-CSF measured by ELISA demonstrated elevated G-CSF levels in WT mice receiving Plcg2S707Y/+ BM cells at day 18 and increasing G-CSF levels at the onset of clinical signs in G-CSF−/− mice receiving Plcg2S707Y/+ BM cells at day 70. f–i, ADVIA analyzer data of the blood at day 18 revealed increased neutrophil/monocyte and reduced lymphocyte counts in WT mice after BM transplantation from Plcg2S707Y/+ mice, while thrombopoiesis and erythropoiesis remained unaltered except for reticulocytes. For all experiments, four mice aged 11 weeks per group were used. Error bars represent the mean ± s.d. in c and the mean ± s.e.m. for the remaining figures. Statistical significance for skin score was determined by a two-way ANOVA and by a paired two-sided t-test for longitudinal weight data. For survival data, statistical significance was determined by a Mantel–Cox test. G-CSF levels and cell numbers between two groups were determined by an unpaired two-sided Student’s t-test. RBC, red blood cell; WBC, white blood cell.
