Both platelet-derived growth factor receptor beta (PDGFRb ) and its' ligand platelet-derived growth factor B-chain are believed to have important roles in vascular developmental and pathological processes, particularly atherosclerosis and angiogenesis. The homozygous disruption of either the receptor or ligand gene is lethal, precluding the use of these mutant animals in the study in adult disease process. To circumvent the lethal phenotypes we created 2 different types of chimeric mice. The first, an aggregation chimera, is made by fusing PDGFRb null morulae with wild-type morulae. The resulting chimeric mouse is viable and is composed of PDGFRb-/- cells and PDGFRb+/+ cells. By examing various tissues in the bodies of these mice it has been shown that that PDGFRb expression during development is important in the development of all muscle lineages and PDGFRb expression by endothelial cells within foreign-body induced granulation tissue formation is important in angiogenesis. We are ccurrently using these aggregation chimeras to test the hypotheses that 1) PDGFRb expression by vascular smooth muscle cells is important in neointima formation in the ligated mouse carotid artery and 2) PDGFRb expression by endothelial cells is important in vascularization of myocardial infarts. To analayze the role of PDGF B-chain we created a different type of chimeric mouse (a tissue specific knockout mouse) by irradiating wild-type mice and reconsituting their hematopoietic system with PDGF B-chain null cells. The resulting mouse is a hematopoietic PDGF B-chain null mouse which lacks PDGF B-chain of hematopoietic origin but still has PDGF B-chain from other cell types. We have shown that the primary source of PDGF B-chain in foreign-body induced granulation tissue is of hematopoietic origin but that vascularity of the granulation tissue in hematopoietic PDGF B-chain null mice is paradoxically increased.