Bone marrow dysfunction in mice lacking the cytokine receptor gp130 in endothelial cells.
In vitro studies suggest that bone marrow endothelial cells contribute to multilineage hematopoiesis, but this function has not been studied in vivo. We used a 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 caused by extramedullary hematopoiesis. The hypocellular marrow contained myeloerythroid 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 gp130 expression in the bone marrow microenvironment, most likely in endothelial cells, makes an important contribution to hematopoiesis.
Yao
Longbiao
L
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th St, Oklahoma City, OK 73104, USA.
Yokota
Takafumi
T
Xia
Lijun
L
Kincade
Paul W
PW
McEver
Rodger P
RP
D000818:Animals; D000831:Animals, Newborn; D001853:Bone Marrow / Q000002:abnormalities* / Q000196:embryology / Q000254:growth & development / Q000503:physiopathology*; D016026:Bone Marrow Transplantation; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D017930:Genes, Reporter / Q000235:genetics; D006410:Hematopoiesis; D051379:Mice; D008822:Mice, Transgenic; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D013997:Time Factors
D050822:Cytokine Receptor gp130; D042787:Receptor, TIE-2