Adult Mice With Targeted Mutation of the Interleukin-11 Receptor (IL11Ra) Display Normal Hematopoiesis

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 α-chain (IL-11Rα). Two genes potentially encode the IL-11Rα: 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-11Rα, 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.

IL‐11 in cardiac and renal fibrosis: Late to the party but a central player

“…Three weeks of daily rmIL-11 treatment in mice activated fibroblasts in the renal interstitium, resulted in deposition of collagen and caused impairment of renal function (Schafer et al, 2017). Similarly, 2 weeks of inducible IL-11 overexpression in a fibroblast-specific manner in murine Il11-transgenic mice crossed with inducible Col1a2-Cre mice caused renal fibrosis and an increase in serum urea and creatinine, indicating renal dysfunction (Schafer et al, 2017 (Nandurkar et al, 1997).…”

Cloning and expression of the first nonmammalian interleukin‐11 gene in rainbow trout Oncorhynchus mykiss

“…Lastly, IL-11 signalling is an absolute requirement for normal development of placentation and survival to birth [18]. Although IL-11R-⁄ -mice display normal hematopoiesis [19], female IL-11R-⁄mice are infertile because of defective decidualization [20] and mutant mice with low IL-11R activity have low fertility [21].…”

Alternatives to platelet transfusions in the management of platelet dysfunction or thrombocytopenia

“…Papilledema has been described in four of 16 children receiving high doses of this agent (100 µ g/kg per day). [34][35][36]…”

“…In one of the earliest approach, augmenting intraplatelet aggregation was achieved by coating red cells with either fibrinogen or fibrinogen peptides. 36 This approach actually permitted correction of the bleeding time in experimental animals. However, no clinical studies were ever attempted.…”