Widespread RSPO3 expression impairs survival. (A) Schematic depicting the generation of our conditional RSPO3 overexpression mouse model. (B) Circulating human RSPO3 (hRSPO3) levels in serum from control and RSPO3 animals measured by using immune-PCR; n = 3 per group. (C) Kaplan-Meyer survival curves for control and RSPO3 animals; n = 12 per group. Representative images of guts (D), hematoxylin, and eosin-stained sternum slides (E), and spleens (F) from control and RSPO3 animals. Rectangles mark regions shown at higher magnification; n = 10 per group. Quantification of white blood cells (WBCs) and major subpopulations (G), platelets (PLT) (H), and RBC and hemoglobin levels (Hb) (I) in the peripheral blood from control and RSPO3 mice. n = 12 for control and n = 10 for RSPO3. (J) Bone marrow cellularity in control and RSPO3 mice (n = 6 per group). Tissues were analyzed 1 month after tamoxifen induction, and data are represented as mean ± standard error of the mean. Two-tailed unpaired t test (panels B, G, H, and J), Mann-Whitney test (panel I), and log-rank test (panel C). Scale bars, 90 μm. BA, basophils; Ct, control; EO, eosinophils; LY, lymphocytes; MO, monocytes; NE, neutrophils; n.s., not significant (P > .05); RSPO3, tamoxifen-induced animals.