Altered Hematopoiesis in Murine Sickle Cell Disease

We investigated the mechanisms of sickle cell disease (SCD) hematopoietic/erythropoietic defects using bone marrow, spleen, and/or peripheral blood from the transgenic SAD mouse model, which closely reproduces the biochemical and physiological disorders observed in human SCD. First, the erythropoietic lineage late precursors (polychromatophilic normoblasts to the intramedullary reticulocytes) of SAD mouse bone marrow were significantly altered morphologi-cally. These anomalies resulted from high levels of hemoglo-bin polymers and were associated with increased cell frag-mentation occurring during medullary endothelial migration of reticulocytes. Secondly, analysis of bone marrow erythro-poiesis in earlier stages showed a marked depletion in SAD erythroid burst-forming units (BFU-E; of,42%) and ery-throid colony-forming units (CFU-E; of,23%) progenitors