Basis of hematopoietic defects in platelet-derived growth factor (PDGF)-B and PDGF beta-receptor null mice

Platelet-derived growth factor (PDGF)-B and PDGF beta -receptor (PDGFR beta ) deficiency in mice is embryonic lethal and results in cardiovascular, ren al, placental, and hematologic disorders. The hematologic disorders are des cribed, and a correlation with hepatic hypocellularity is demonstrated. To explore possible causes, the colony-forming activity of fetal liver cells i n vitro was assessed, and hematopoietic chimeras were demonstrated by the t ransplantation of mutant fetal liver cells into lethally irradiated recipie nts. It was found that mutant colony formation is equivalent to that of wil d-type controls. Hematopoietic chimeras reconstituted with PDGFB(-/-), PDGF R beta (-/-), or wild-type fetal river cells show complete engraftment (gre ater than 98%) with donor granulocytes, monocytes, B cells, and T cells and display none of the cardiovascular or hematologic abnormalities seen in mu tants. In mouse embryos, PDGF-B is expressed by vascular endothelial cells and megakaryocytes. After birth, expression is seen in macrophages and neur ons. This study demonstrates that hematopoietic PDGF-B or PDGFR beta expres sion is not required for hematopoiesis or integrity of the cardiovascular s ystem. It is argued that metabolic stress arising from mutant defects in th e placenta, heart, or blood vessels may lead to impaired liver growth and d ecreased production of blood cells. The chimera models in this study will s erve as valuable tools to test the role of PDGF in inflammatory and immune responses. (Blood. 2001;97:1990-1998) (C) 2001 by The American Society of H ematology.