Conditional Vascular Cell Adhesion Molecule 1 Deletion in Mice

Abstract

We generated vascular cell adhesion molecule (VCAM)-1 “knock-in” mice and Cre recombinase transgenic mice to delete the VCAM-1 gene ( vcam-1 ) in whole mice, thereby overcoming the embryonic lethality seen with conventional vcam-1 –deficient mice. vcam-1 knock-in mice expressed normal levels of VCAM-1 but showed loss of VCAM-1 on endothelial and hematopoietic cells when interbred with a “TIE2Cre” transgene. Analysis of peripheral blood from conditional vcam-1– deficient mice revealed mild leukocytosis, including elevated immature B cell numbers. Conversely, the bone marrow (BM) had reduced immature B cell numbers, but normal numbers of pro-B cells. vcam-1 –deficient mice also had reduced mature IgD 1 B and T cells in BM and a greatly reduced capacity to support short-term migration of transferred B cells, CD4 1 T cells, CD8 1 T cells, and preactivated CD4 1 T cells to the BM. Thus, we report an until now unappreciated dominant role for VCAM-1 in lymphocyte homing to BM.