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目的：构建红细胞分化相关基因（ EDAG）敲除小鼠并研究其对低剂量辐射损伤的敏感性。方法利用锌指核酸酶技术（ ZFNs）建立EDAG敲除小鼠模型；通过外周血细胞计数、骨髓细胞的DNA损伤和集落形成能力评价低剂量辐射损伤。对野生型及EDAG敲除小鼠进行剂量率为0．31 Gy／min的X线照射，1 min／d，连续照射7 d，小鼠累计照射剂量为2．17 Gy。在X线照射后第1、3、5、7天称重并进行血常规检测（n＝7）；照射后第3天分离小鼠骨髓细胞，利用免疫荧光实验检测DNA损伤标志物p-H2A．x的表达水平（ n＝3）；照射后第5天分离小鼠骨髓细胞，接种集落并于7 d后进行集落计数（ n＝3）。结果成功建立了EDAG敲除小鼠模型并在蛋白水平进行了敲除效果的鉴定；X线照射后第3天，与野生型相比，EDAG敲除小鼠白细胞明显减少，敲除小鼠骨髓细胞DNA损伤标志物p-H2A．x表达水平增加；X线照射7 d后骨髓细胞的集落形成能力降低。结论研究发现EDAG敲除小鼠对低剂量辐射诱导的损伤更加敏感，表现为血细胞数量减少，骨髓细胞成集落能力下降，DNA损伤增加。表明EDAG敲除小鼠作为一种对辐射高度敏感的动物模型，可作为低剂量辐射损伤生物学效应评价的有力工具。“,”Objective To generate the erythroid differentiation associated gene(EDAG) knockout mice and analyze their sensitivity to low dose radiation-induced damage.Methods Zinc finger nuclease technology ( ZFNs ) was used to produce the EDAG knockout mice.The low dose radiation-induced damage was evaluated by peripheral blood cell counts, DNA damage and colony formation of bone marrow cells.Wild-type and EDAG knockout mice were irradiated with 0.31 Gy/min X-ray, one minute per day for seven consecutive days, and the cumulative radiation dose was 2.17 Gy(n=7).The blood cell counts were measured by an automated hemocytometer.DNA damage was detected by immunofluorescence assay with a DNA damage marker p-H2A.x antibody (n=3).The colony formation ability of bone marrow cells was evaluated with a semi-solid culture medium(n=3).Results A model of EDAG knockout mice was established.Compared to wide type mice, white blood cell counts of EDAG knockout mice decreased significantly while the DNA damage marker p-H2A.x expression was increased on the third day after X-ray irradiation.The ability of colony-forming was reduced after 7 days of X-ray irradiation.Conclusion Our present study found that EDAG knockout mice are more sensitive to low dose radiation-induced damage as shown by decreased peripheral blood cells counts, reduced colony-forming ability of bone marrow cells, and increased DNA damage.These results suggest that EDAG knockout mice can serve as a powerful tool for evaluation of the biological effects of low-dose radiation damage.