Histopathology of blood, spleen, and liver of humanized HbA control and CA mice before and after transfusion. Peripheral blood smears of untransfused CA mice exhibit severe anemia compared with HbA littermate control mice. There are significant numbers of reticulocytes, circulating erythroblasts, and microcytic, hypochromic, and fragmented RBCs in untransfused CA mouse blood. In addition, the normal structure of red pulp and white pulp in the spleen is absent. In the liver of untransfused CA mice, there are extensive clusters of extramedullary hematopoiesis and increased iron staining. In contrast, the hypertransfused CA mouse has a normal peripheral blood smear and greatly improved histology similar to the HbA control, except excess iron is present in the liver. Hypotransfused CA mice are still anemic, have significant numbers of erythroblasts and thalassemic RBCs in the blood, and have a histopathology similar to the untransfused CA mouse. All mice are 8 weeks of age, except for the untransfused CA mouse, which is only 2 weeks old. Scale bars: blood smear, 10 μm; spleen, 100 μm; liver (low power), 50 μm; liver (high power), 10 μm; liver iron, 50 μm.