The el20 mutation leads to loss of expression of both SHIP1 and the s-SHIP isoform. (A) Quantitative RT-PCR for s-SHIP mRNA expression in wild-type sorted hematopoietic cell subsets. Sorted cell subsets were obtained from pools of at least 3 mice. All values have been normalized to expression of HPRT. LKS indicates lineage⁻c-Kit⁺Sca-1⁺; LK, lineage⁻c-Kit⁺; DN, CD4⁻CD8⁻ double-negative thymocytes; and DP, CD4⁺CD8⁺ double-positive thymocytes. (B) Quantitative RT-PCR for s-SHIP and SHIP1 mRNA expression in BMMΦs from wild-type SHIP1^+/+, SHIP1^−/−, SHIP1^el20/el20, and compound heterozygous SHIP1^−/el20 mice. All values have been normalized to expression of HPRT. Bar graphs represent the mean ± SD of 4 samples for each genotype. ***P < .0001 using log-rank (Mantel Cox) test compared with SHIP1^+/+ control. (C) Representative dot plots of bone marrow pre-B cells (top panel) and thymic T-cell subsets (bottom panel). The mean proportion for each subset was gated on live hematopoietic cells and calculated from at least 3 mice of each genotype. (D) IL-6 levels in serum of age-matched SHIP1^−/el20 mice compared with SHIP1^+/+, SHIP1^−/−, and SHIP1^el20/el20 mice shown in Figure 5A. **P < .01 by 2-tailed Mann-Whitney test. (E) IL-6 production by resting SHIP1^−/el20 BMMΦs compared with SHIP1^+/+, SHIP1^−/−, and SHIP1^el20/el20 samples shown in Figure 5B. *P < .05, 2-tailed Mann-Whitney test. ND indicates not detected. (F) Hematoxylin and eosin-stained histologic sections showing normal lungs at 6 weeks of age but consolidation of alveolar airspaces in 11-week-old SHIP1^−/el20 lungs. (G) Improved survival of SHIP1^−/el20 mice compared with SHIP1^el20/el20 mice. Results for all other mice reproduced from Figure 2C. ***P < .0001 using log-rank (Mantel Cox) test. NS indicates not significant.