HbSC and HbSS mice exhibit distinct hematological properties. (A) Schematic representation of the generation of humanized HbSC mice. (B-G) Hematological indices in 4-month-old HbAA (n = 8; sex combined), HbSC (n = 19; sex combined), and HbSS mice (n = 12; sex combined) for Hb levels (B), hematocrit (C), reticulocyte counts (D), RBC counts (E), CHCM (F), and white blood cell (WBC) counts (G). (H) Shortened RBC life span in HbSC and HbSS mice. (I) Representative peripheral blood smears from C57BL/6, HbAA, HbSC, and HbSS mice. Thick arrows indicate target cells; hollow arrows, HbC crystal; thin arrow, double dimple cell; and double arrowhead, sickle cell. (J) Percoll density gradient analysis showing dense RBCs in HbSC mice. Hypodense RBCs apparent in HbSS mice probably represent reticulocytes. Comparisons to HbAA mice are indicated in green; comparisons between HbSC and HbSS mice are indicated in blue. Scale bars, 20 μm. Data are presented as mean ± standard deviation. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. CHCM, cellular Hb concentration mean; ns, no significant difference; RBC, red blood cell; Reti, reticulocyte.