【Animal modeling】-Effect of -FOXO3A on radiation injury of hematopoietic system in mice with total body irradiation

  Objective: To investigate the effect of FOXO3A on ionizing radiation injury in the hematopoietic system using FOXO3A knockout mice.

  Methods: FOXO3A-/- mice and WT mice (FVB/N) were divided into wild-type mice control group (WT group), FOXO3A-/- mice control group (FOXO3A-/- group), wild-type mice The four groups, the irradiation group (WT+IR) and the FOXO3A-/- mouse irradiation group (FOXO3A-/-+IR), received sham irradiation and 4 Gy X-ray total body irradiation (TBI), respectively, with a dose rate of 0.9 Gy /min. 14 days after receiving TBI, the organ index, peripheral blood and bone marrow cell counts, bone marrow cell types, hematopoietic progenitor cells (HPCs) granulocyte macrophage colony forming units (colony forming units) were detected in FOXO3A-/- mice and WT mice. The ability of forming unit-granulocyte and macrophage, CFU-GM) to form, and the effect of FOXO3A gene knockout on radiation damage of hematopoietic system was observed.

  Results: Under physiological conditions, the count of nucleated cells in the bone marrow of FOXO3A-/- mice decreased and the proportion of HPCs increased (P<0.05); 14 days after the mice received 4GyX-ray TBI, FOXO3A gene knockout would aggravate the ionizing radiation-induced HPCs and HPCs. The proportion of hematopoietic stem cells (HSCs) decreased, but also suppressed the radiation-induced decrease in the number of nucleated cells in the bone marrow and the decreased ability of hematopoietic progenitor cells to form CFU-GM.

  CONCLUSION: FOXO3A gene knockout disrupts the maintenance of hematopoietic system homeostasis, aggravates the radiation damage of HPCs and HSCs in TBI mice, and has a certain impact on the radiation sensitivity of hematopoietic cells. The regulatory role of FOXO3A in the ionizing radiation injury of the hematopoietic system and whether it can act as a Targets for injury prevention and treatment remain to be further investigated.