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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4093-4101.
Prepublished online as a Blood First Edition Paper on August 23, 2005; DOI 10.1182/blood-2005-02-0671.
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Submitted February 17, 2005
Accepted August 10, 2005
Bone marrow dysfunction in mice lacking the cytokine receptor gp130 in endothelial cells
Longbiao Yao, Takafumi Yokota, Lijun Xia, Paul W Kincade, and Rodger P McEver*
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
* Corresponding author; email: rodger-mcever{at}omrf.ouhsc.edu.
In vitro studies suggest that bone marrow endothelial cells contribute to multilineage hematopoiesis, but this function has not been studied in vivo. We used Cre/loxP-mediated recombination to produce mice that lacked the cytokine receptor subunit gp130 in hematopoietic and endothelial cells. Although normal at birth, the mice developed bone marrow dysfunction that was accompanied by splenomegaly due to extramedullary hematopoiesis. The hypocellular marrow contained myelo-erythroid progenitors and functional repopulating stem cells. However, long-term bone marrow cultures produced few hematopoietic cells despite continued expression of gp130 in most stromal cells. Transplanting gp130-deficient bone marrow into irradiated wild-type mice conferred normal hematopoiesis, whereas transplanting wild-type bone marrow into irradiated gp130-deficient mice did not cure the hematopoietic defects. These data provide evidence that expression of gp130 in the bone marrow microenvironment, most likely in endothelial cells, makes an important contribution to hematopoiesis.
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