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| Adult mice with targeted mutation of the interleukin-11 receptor (IL11Ra) display normal hematopoiesis |
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| Author(s): Nandurkar HH, Robb L, Tarlinton D, Barnett L, Kontgen F, Begley CG |
| Source: BLOOD Volume: 90 Issue: 6 Pages: 2148-2159 Published: SEP 15 1997 |
| Times Cited: 65 References: 82 |
| Abstract: 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. (C) 1997 by The American Society of Hematology. |
| Document Type: Article |
| Language: English |
| Reprint Address: Nandurkar, HH (reprint author), ROYAL MELBOURNE HOSP, WALTER & ELIZA HALL INST MED RES, PARKVILLE, VIC 3050 AUSTRALIA |
Addresses:
1. ROYAL MELBOURNE HOSP, COOPERAT CTR CELLULAR GROWTH FACTORS, PARKVILLE, VIC 3050 AUSTRALIA
2. ROYAL MELBOURNE HOSP, ROTARY BONE MARROW RES LABS, PARKVILLE, VIC 3050 AUSTRALIA |
| Publisher: W B SAUNDERS CO, INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 |
| Subject Category: Hematology |
| IDS Number: XW306 |
| ISSN: 0006-4971 |
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