Impaired hematopoiesis and delayed thrombopoietic recovery following sublethal irradiation in SRC-3 knockout mice

Abstract

The objective of the present study was to investigate the role of the steroid receptor coactivator-3 (SRC-3) in hematopoiesis of mouse bone marrow (BM) following total body irradiation (TBI). SRC-3−/− mice and wild-type (WT) mice were exposed to 4.5 Gy γ rays. Immunoblotting analysis revealed that the SRC-3 protein (p160) levels in normal BM-nucleated cells in WT were higher than in SRC-3−/− mice. Furthermore, peripheral blood cell counts, BM cellularity and colony-forming unit (CFU) assays were performed following irradiation. The results showed that peripheral blood cells were significantly lower in number and recovered less rapidly in irradiated SRC-3−/− mice as compared with control animals. BM-nucleated cell and CFU counts were significantly decreased in SRC-3−/− mice on the 7th and 14th day. Of note, the recovery of platelet (PLT) and megakaryocytic lineage were more depressed than the granulocytic and erythroid lineage in SRC-3−/− mice. In conclusion, the present study demonstrated that the hematopoietic ability in SRC-3 knockout mice is severely impaired following a sublethal dose of irradiation.