Genetic evidence for functional redundancy of platelet/endothelial cell adhesion molecule-1 (PECAM-1): CD31-deficient mice reveal PECAM-1-dependent and PECAM-1-independent functions

Platelet/endothelial cell adhesion molecule-1 (PECAM-1; CD31), a member of the Ig superfamily, is expressed strongly at endothelial cell-cell junction s, on platelets, and on most leukocytes, CD31 has been postulated to play a role in vasculogenesis and angiogenesis, and has been implicated as a hey mediator of the transendothelial migration of leukocytes, To further define the physiologic role of CD31, we used targeted gene disruption of the CD31 gene in embryonic stem cells to generate CD31-deficient mice. CD31-deficie nt mice (CD31KO) are viable and born at the expected Mendelian frequency, r emain healthy, and exhibit no obvious vascular developmental defects. In re sponse to inflammatory challenge, polymorphonuclear leukocytes of CD31KO mi ce are arrested between the vascular endothelium and the basement membrane of inflammatory site mesenteric microvessels, confirming a role for CD31 in the migration of neutrophils through the subendothelial extracellular matr ix. Normal numbers of leukocytes are recovered from inflammatory sites in C D31KO mice, however, suggesting that the defect in leukocyte migration acro ss basal lamina observed in the absence of CD31 may be compensated for by t he use of other adhesion molecules, or possibly an increased rate of migrat ion. Homing of T lymphocytes in vivo is normal, and CD31KO mice are able to mount a cutaneous hypersensitivity response normally, In addition, CD31-me diated hemophilic adhesion does not appear to play a role in platelet aggre gation in vitro. This study provides genetic evidence that CD31 is involved in transbasement membrane migration, but does not play an obligatory role in either vascular development or leukocyte migration.