Zhang Ling, Sun Zhao, Shen Ai-Ling, Ma Li, Jiang Xue-Ying, Ma Guan-Jie, Yang Xiao, Zhao Chun-Hua
State Key Lab of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, Tianjin 300020, China.
Sheng Wu Gong Cheng Xue Bao. 2003 Jul;19(4):428-32.
The effects of the Smad3- knockout on the hematopoiesis of mouse were investigated in this work. Five pairs of wild type and Smad3- null mice were studied. White blood cell(WBC), red blood cell(RBC) and platelet (PLT) counting of peripheral blood cells were performed with blood obtained from tails. And white blood cells were classified by their morphology. Bone marrow nucleated cells (BMNCs) were counted and classified. The CFU-GM, BFU-E, CFU-GEMM yields were measured in each pair of mice. CFU-S yield of each mouse was measured by injecting bone marrow cells into lethally irradiated 8-10 weeks old wild type female mice. And the pathomorphism of their bone marrows, spleens and livers were observed. As a result, WBC and PLT of Smad3- null mice were significantly higher than those in wild type mice. Smad3- null mice had much more proportion of granulocytes in classification. There wasn't any difference in RBC counting and BFU-E measurement. The yield of CFU-GM increased, while the yields of CFU-GEMM and CFU-S markedly reduced. Bone marrows are actively proliferative, with granulocytosis. The granulocyte/erythrocyte ratio increased. There were no obviously alterative in spleen and liver. Thus Smad3- knockout results in a decreased number of stem and progenitor cells. Moreover hematopoietic differentiation is abnormal with a tendency to forming more granulocytes and platelets. The effect of Smad3 on hematopoiesis is correlative to that of TGF-beta.
本研究探讨了Smad3基因敲除对小鼠造血功能的影响。研究了五对野生型和Smad3基因缺失小鼠。采集小鼠尾血,进行外周血细胞白细胞(WBC)、红细胞(RBC)和血小板(PLT)计数,并对白细胞进行形态学分类。计数并分类骨髓有核细胞(BMNCs)。检测每对小鼠的CFU-GM、BFU-E、CFU-GEMM产量。将骨髓细胞注射到经致死剂量照射的8-10周龄野生型雌性小鼠体内,检测每只小鼠的CFU-S产量。观察其骨髓、脾脏和肝脏的病理形态。结果显示,Smad3基因缺失小鼠的白细胞和血小板明显高于野生型小鼠。Smad3基因缺失小鼠分类中粒细胞比例更高。红细胞计数和BFU-E检测无差异。CFU-GM产量增加,而CFU-GEMM和CFU-S产量显著降低。骨髓呈活跃增殖状态,粒细胞增多。粒细胞/红细胞比值增加。脾脏和肝脏无明显改变。因此,Smad3基因敲除导致干细胞和祖细胞数量减少。此外,造血分化异常,倾向于形成更多的粒细胞和血小板。Smad3对造血的影响与TGF-β相关。