Homozygous SHIP1^el20/el20 mice have runting, early lethality, and severe lung disease. (A) Five-week-old sex-matched littermates showing runting of a homozygous SHIP1^el20/el20 mouse compared with wild-type SHIP1^+/+ and heterozygous SHIP1^+/el20 mice. (B) Total body weight (TBW) of male SHIP1^el20/el20 mice compared with male SHIP1^+/+ controls. ***P < .001 using 1-way ANOVA. (C) Survival curves of SHIP1^el20/el20 mice compared with SHIP1^−/− and SHIP1^+/el20 mice. ***P < .0001 using log-rank (Mantel Cox) test. (D) Hematoxylin and eosin–stained histologic lung sections of 4-week-old SHIP1^el20/el20 mice showing alveolar airspace consolidation of lungs with macrophages containing eosinophilic Ym1 crystals (arrows). Normal lungs from age-matched SHIP1^+/+ and SHIP1^−/− mice are shown.