Nandurkar H H, Robb L, Tarlinton D, Barnett L, Köntgen F, Begley C G
The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Victoria, Australia.
Blood. 1997 Sep 15;90(6):2148-59.
Interleukin-11 (IL-11) is a pleiotropic growth factor with a prominent effect on megakaryopoiesis and thrombopoiesis. The receptor for IL-11 is a heterodimer of the signal transduction unit gp130 and a specific receptor component, the alpha-chain (IL-11R alpha). Two genes potentially encode the IL-11R alpha: the IL11Ra and IL11Ra2 genes. The IL11Ra gene is widely expressed in hematopoietic and other organs, whereas the IL11Ra2 gene is restricted to only some strains of mice and its expression is confined to testis, lymph node, and thymus. To investigate the essential actions mediated by the IL-11R alpha, we have generated mice with a null mutation of IL11Ra (IL11Ra-/-) by gene targeting. Analysis of IL11Ra expression by Northern blot and reverse transcriptase-polymerase chain reaction, as well as the absence of response of IL11Ra-/- bone marrow cells to IL-11 in hematopoietic assays, further confirmed the null mutation. Compensatory expression of the IL11Ra2 in bone marrow cells was not detected. IL11Ra-/- mice were healthy with normal numbers of peripheral blood white blood cells, hematocrit, and platelets. Bone marrow and spleen contained normal numbers of cells of all hematopoietic lineages, including megakaryocytes. Clonal cultures did not identify any perturbation of granulocyte-macrophage (GM), erythroid, or megakaryocyte progenitors. The number of day-12 colony-forming unit-spleen progenitors were similar in wild-type and IL11Ra-/- mice. The kinetics of recovery of peripheral blood white blood cells, platelets, and bone marrow GM progenitors after treatment with 5-flurouracil were the same in IL11Ra-/- and wild-type mice. Acute hemolytic stress was induced by phenylhydrazine and resulted in a 50% decrease in hematocrit. The recovery of hematocrit was comparable in IL11Ra-/ - and wild-type mice. These observations indicate that IL-11 receptor signalling is dispensable for adult hematopoiesis.
白细胞介素-11（IL-11）是一种多效生长因子，对巨核细胞生成和血小板生成具有显著影响。IL-11的受体是信号转导单位gp130与特定受体成分α链（IL-11Rα）的异二聚体。有两个基因可能编码IL-11Rα：IL11Ra和IL11Ra2基因。IL11Ra基因在造血器官和其他器官中广泛表达，而IL11Ra2基因仅在某些小鼠品系中存在，其表达局限于睾丸、淋巴结和胸腺。为了研究IL-11Rα介导的重要作用，我们通过基因打靶构建了IL11Ra基因敲除（IL11Ra-/-）小鼠。通过Northern印迹和逆转录-聚合酶链反应分析IL11Ra的表达，以及在造血试验中IL11Ra-/-骨髓细胞对IL-11无反应，进一步证实了基因敲除。未检测到骨髓细胞中IL11Ra2的代偿性表达。IL11Ra-/-小鼠健康，外周血白细胞、血细胞比容和血小板数量正常。骨髓和脾脏中所有造血谱系的细胞数量正常，包括巨核细胞。克隆培养未发现粒细胞-巨噬细胞（GM）、红系或巨核细胞祖细胞有任何扰动。野生型和IL11Ra-/-小鼠中第12天脾集落形成单位祖细胞的数量相似。用5-氟尿嘧啶治疗后，IL11Ra-/-和野生型小鼠外周血白细胞、血小板和骨髓GM祖细胞的恢复动力学相同。苯肼诱导急性溶血应激，导致血细胞比容降低50%。IL11Ra-/-和野生型小鼠的血细胞比容恢复情况相当。这些观察结果表明，IL-11受体信号传导对于成年造血是可有可无的。
