|
|
 Previous Article | Table of Contents | Next Article 
RAPID COMMUNICATION
Adult Mice With Targeted Mutation of the Interleukin-11 Receptor (IL11Ra) Display Normal Hematopoiesis
Harshal H. Nandurkar,
Lorraine Robb,
David Tarlinton,
Louise Barnett,
Frank Köntgen, and
C. Glenn Begley
From The Walter and Eliza Hall Institute of Medical Research, The Cooperative Centre for Cellular Growth Factors, and The Rotary Bone Marrow Research Laboratories, The Royal Melbourne Hospital, Victoria, Australia.
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  -chain (IL-11R). Two genes potentially encode the IL-11R: 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, 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.
Blood, Vol. 90 No. 6 (September 15), 1997:
pp. 2148-2159
© 1997 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. T. Gurfein, Y. Zhang, C. B. Lopez, A. T. Argaw, A. Zameer, T. M. Moran, and G. R. John
IL-11 Regulates Autoimmune Demyelination
J. Immunol.,
October 1, 2009;
183(7):
4229 - 4240.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Menkhorst, L. Salamonsen, L. Robb, and E. Dimitriadis
IL11 Antagonist Inhibits Uterine Stromal Differentiation, Causing Pregnancy Failure in Mice
Biol Reprod,
May 1, 2009;
80(5):
920 - 927.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Hams, C. S. Colmont, V. Dioszeghy, V. J. Hammond, C. A. Fielding, A. S. Williams, M. Tanaka, A. Miyajima, P. R. Taylor, N. Topley, et al.
Oncostatin M Receptor-{beta} Signaling Limits Monocytic Cell Recruitment in Acute Inflammation
J. Immunol.,
August 1, 2008;
181(3):
2174 - 2180.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Blank, G. Karlsson, and S. Karlsson
Signaling pathways governing stem-cell fate
Blood,
January 15, 2008;
111(2):
492 - 503.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Jenkins, A. W. Roberts, C. J. Greenhill, M. Najdovska, T. Lundgren-May, L. Robb, D. Grail, and M. Ernst
Pathologic consequences of STAT3 hyperactivation by IL-6 and IL-11 during hematopoiesis and lymphopoiesis
Blood,
March 15, 2007;
109(6):
2380 - 2388.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Bao, S. Devi, J. Bowen-Shauver, S. Ferguson-Gottschall, L. Robb, and G. Gibori
The Role of Interleukin-11 in Pregnancy Involves Up-Regulation of {alpha}2-Macroglobulin Gene through Janus Kinase 2-Signal Transducer and Activator of Transcription 3 Pathway in the Decidua
Mol. Endocrinol.,
December 1, 2006;
20(12):
3240 - 3250.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Cho, M. J. Kang, R. J. Homer, H. R. Kang, X. Zhang, P. J. Lee, J. A. Elias, and C. G. Lee
Role of Early Growth Response-1 (Egr-1) in Interleukin-13-induced Inflammation and Remodeling
J. Biol. Chem.,
March 24, 2006;
281(12):
8161 - 8168.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Chen, L. Rabach, P. Noble, T. Zheng, C. G. Lee, R. J. Homer, and J. A. Elias
IL-11 Receptor {alpha} in the Pathogenesis of IL-13-Induced Inflammation and Remodeling
J. Immunol.,
February 15, 2005;
174(4):
2305 - 2313.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. P.M van Empel and L. J De Windt
Myocyte hypertrophy and apoptosis: a balancing act
Cardiovasc Res,
August 15, 2004;
63(3):
487 - 499.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Fuchs, H. D. Xiao, J. M. Cole, J. W. Adams, K. Frenzel, A. Michaud, H. Zhao, G. Keshelava, M. R. Capecchi, P. Corvol, et al.
Role of the N-terminal Catalytic Domain of Angiotensin-converting Enzyme Investigated by Targeted Inactivation in Mice
J. Biol. Chem.,
April 16, 2004;
279(16):
15946 - 15953.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. C. Zhang and H. F. Lodish
Insulin-like growth factor 2 expressed in a novel fetal liver cell population is a growth factor for hematopoietic stem cells
Blood,
April 1, 2004;
103(7):
2513 - 2521.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Tanaka, Y. Hirabayashi, T. Sekiguchi, T. Inoue, M. Katsuki, and A. Miyajima
Targeted disruption of oncostatin M receptor results in altered hematopoiesis
Blood,
November 1, 2003;
102(9):
3154 - 3162.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Tarlinton, A. Light, D. Metcalf, R. P. Harvey, and L. Robb
Architectural Defects in the Spleens of Nkx2-3-Deficient Mice Are Intrinsic and Associated with Defects in Both B Cell Maturation and T Cell-Dependent Immune Responses
J. Immunol.,
April 15, 2003;
170(8):
4002 - 4010.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Tolosano, S. Fagoonee, E. Hirsch, F. G. Berger, H. Baumann, L. Silengo, and F. Altruda
Enhanced splenomegaly and severe liver inflammation in haptoglobin/hemopexin double-null mice after acute hemolysis
Blood,
December 1, 2002;
100(12):
4201 - 4208.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Kuter and C. G. Begley
Recombinant human thrombopoietin: basic biology and evaluation of clinical studies
Blood,
November 15, 2002;
100(10):
3457 - 3469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kirito, M. Osawa, H. Morita, R. Shimizu, M. Yamamoto, A. Oda, H. Fujita, M. Tanaka, K. Nakajima, Y. Miura, et al.
A functional role of Stat3 in in vivo megakaryopoiesis
Blood,
May 1, 2002;
99(9):
3220 - 3227.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Nakano and M. D. Gunn
Gene Duplications at the Chemokine Locus on Mouse Chromosome 4: Multiple Strain-Specific Haplotypes and the Deletion of Secondary Lymphoid-Organ Chemokine and EBI-1 Ligand Chemokine Genes in the plt Mutation
J. Immunol.,
January 1, 2001;
166(1):
361 - 369.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Gainsford, H. Nandurkar, D. Metcalf, L. Robb, C. G. Begley, and W. S. Alexander
The residual megakaryocyte and platelet production in c-Mpl-deficient mice is not dependent on the actions of interleukin-6, interleukin-11, or leukemia inhibitory factor
Blood,
January 15, 2000;
95(2):
528 - 534.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Opal, J. W. Jhung, J. C. Keith Jr, S. J. Goldman, J. E. Palardy, and N. A. Parejo
Additive Effects of Human Recombinant Interleukin-11 and Granulocyte Colony-Stimulating Factor in Experimental Gram-Negative Sepsis
Blood,
May 15, 1999;
93(10):
3467 - 3472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. A.K. Betz, W. Bloch, M. van den Broek, K. Yoshida, T. Taga, T. Kishimoto, K. Addicks, K. Rajewsky, and W. Muller
Postnatally Induced Inactivation of gp130 in Mice Results in Neurological, Cardiac, Hematopoietic, Immunological, Hepatic, and Pulmonary Defects
J. Exp. Med.,
November 16, 1998;
188(10):
1955 - 1965.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Peters, A. M. Muller, and S. Rose-John
Interleukin-6 and Soluble Interleukin-6 Receptor: Direct Stimulation of gp130 and Hematopoiesis
Blood,
November 15, 1998;
92(10):
3495 - 3504.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Bilinski, D. Roopenian, and A. Gossler
Maternal IL-11Ralpha function is required for normal decidua and fetoplacental development in mice
Genes & Dev.,
July 15, 1998;
12(14):
2234 - 2243.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. Kaushansky
Thrombopoietin and the Hematopoietic Stem Cell
Blood,
July 1, 1998;
92(1):
1 - 3.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Gainsford, A. W. Roberts, S. Kimura, D. Metcalf, G. Dranoff, R. C. Mulligan, C. G. Begley, L. Robb, and W. S. Alexander
Cytokine Production and Function in c-mpl-Deficient Mice: No Physiologic Role for Interleukin-3 in Residual Megakaryocyte and Platelet Production
Blood,
April 15, 1998;
91(8):
2745 - 2752.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
