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Blood, 1 April 2001, Vol. 97, No. 7, pp. 1990-1998
HEMATOPOIESIS
Basis of hematopoietic defects in platelet-derived growth factor
(PDGF)-B and PDGF -receptor null mice
Wolfgang E. Kaminski,
Per Lindahl,
Nancy L. Lin,
Virginia C. Broudy,
Jeffrey R. Crosby,
Mats Hellström,
Birgitta Swolin,
Daniel F. Bowen-Pope,
Paul J. Martin,
Russell Ross,
Christer Betsholtz, and
Elaine
W. Raines
From the Departments of Pathology and Medicine,
University of Washington School of Medicine; the Division of Clinical
Research, Fred Hutchinson Cancer Research Center, Seattle, WA; the
Department of Medical Biochemistry, University of Göteborg; and
the Department of Clinical Chemistry, Sahlgrenska Hospital,
Göteborg, Sweden.
Platelet-derived growth factor (PDGF)-B and PDGF -receptor
(PDGFR ) deficiency in mice is embryonic lethal and results in cardiovascular, renal, placental, and hematologic disorders. The hematologic disorders are described, and a correlation with hepatic hypocellularity is demonstrated. To explore possible causes, the colony-forming activity of fetal liver cells in vitro was
assessed, and hematopoietic chimeras were demonstrated by the
transplantation of mutant fetal liver cells into lethally irradiated
recipients. It was found that mutant colony formation is equivalent to
that of wild-type controls. Hematopoietic chimeras reconstituted with PDGF-B / , PDGFR / , or wild-type fetal
liver cells show complete engraftment (greater than 98%) with donor
granulocytes, monocytes, B cells, and T cells and display none of the
cardiovascular or hematologic abnormalities seen in mutants. In mouse
embryos, PDGF-B is expressed by vascular endothelial cells and
megakaryocytes. After birth, expression is seen in macrophages and
neurons. This study demonstrates that hematopoietic PDGF-B or PDGFR
expression is not required for hematopoiesis or integrity of the
cardiovascular system. It is argued that metabolic stress arising from
mutant defects in the placenta, heart, or blood vessels may lead to
impaired liver growth and decreased production of blood cells. The
chimera models in this study will serve as valuable tools to test the
role of PDGF in inflammatory and immune responses.

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