Chronic exposure to retroviral vector encoded MGDF (mpl-ligand) induces lineage-specific growth and differentiation of megakaryocytes in mice.
Chronic exposure to retroviral vector encoded MGDF (mpl-ligand) induces lineage-specific growth and differentiation of megakaryocytes in mice.
复制标题
长期暴露于编码 MGDF（mpl-配体）的逆转录病毒载体可诱导小鼠巨核细胞的谱系特异性生长和分化。
作者：
X. Q. Yan;D. Lacey;F. Fletcher;C. Hartley;P. McElroy;Yu Sun;Min Xia;S. Mu;C. Saris;D. Hill;R. Hawley;I. Mcniece
巨核细胞生长发育因子（MGDF）最近被确定为c-mpl受体的配体。利用逆转录病毒介导的基因转移，MGDF在小鼠中过度表达，以评估慢性暴露于这种生长因子的系统性影响。MGDF过表达小鼠移植后血小板恢复速度快于对照小鼠。在这种恢复之后，这些动物的血小板水平继续增加到正常基线水平的4到8倍，并保持升高（比对照小鼠高5倍），这些动物在移植后4个多月存活且健康。在这些小鼠的许多器官中，包括骨髓、脾脏、肝脏和淋巴结，检测到巨核细胞数量增加。MGDF的长期过度表达导致骨髓造血减少，尤其是红细胞造血，并向脾和肝的髓外造血转移。迄今为止分析的所有MGDF过表达小鼠都发生了骨髓纤维化和骨硬化，可能是由巨核细胞和血小板产生的细胞因子引起的。MGDF过表达小鼠对其他造血谱系没有明显影响，表明MGDF在体内的刺激作用仅限于巨核细胞谱系。
Megakaryocyte growth and development factor (MGDF) has recently been identified as a ligand for the c-mpl receptor. Using retroviral-mediated gene transfer, MGDF has been overexpressed in mice to evaluate the systematic effects due to chronic exposure to this growth factor. MGDF overexpressing mice had more rapid platelet recovery than control mice after transplantation. Following this recovery, the platelet levels continued increasing to fourfold to eightfold above normal baseline levels and remained elevated (five-fold above control mice) in these animals, which are alive and well at more than 4 months posttransplantation. Increased megakaryocyte numbers were detected in a number of organs in these mice including bone marrow, spleen, liver, and lymph nodes. Prolonged overexpression of MGDF led to decreased marrow hematopoiesis, especially erythropoiesis, with a shift to extramedullary hematopoiesis in the spleen and liver. All the MGDF overexpressing mice analyzed to date developed myelofibrosis and osteosclerosis, possibly induced by megakaryocyte and platelet produced cytokines. No significant effect on other hematopoietic lineages was seen in the MGDF overexpressing mice, showing that the stimulatory effect of MGDF in vivo is restricted to the megakaryocyte lineage.
由多聚脑脊液 (IL-3) 表达失调引起的非肿瘤性造血骨髓增殖综合征。
影响因子：
20.3
作者：
Chang,JM;Metcalf,D;Lang,RA;Gonda,TJ;Johnson,GR
通讯作者：
Johnson,GR