Conditional Vascular Cell Adhesion Molecule 1 Deletion in Mice: Impaired Lymphocyte Migration to Bone Marrow

doi:10.1084/jem.193.6.741

Published online 19 March 2001.

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© The Rockefeller University Press, 0022-1007/2001/3/741/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 6, March 19, 2001 741-754

Original Article

Conditional Vascular Cell Adhesion Molecule 1 Deletion in Mice: Impaired Lymphocyte Migration to Bone Marrow

Pandelakis A. Koni^a, Sunil K. Joshi^a, Ulla-Angela Temann^b, Dian Olson^d, Linda Burkly^d, and Richard A. Flavell^b,c
^a Molecular Immunology Program, Institute of Molecular Medicine and Genetics, and Department of Medicine, Medical College of Georgia, Augusta, Georgia 30912
^b Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520
^c Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520
^d Biogen Incorporated, Boston, Massachusetts 02142

Correspondence to: Pandelakis A. Koni, Rm. CA2007, Institute of Molecular Medicine and Genetics, Medical College of Georgia, 1120 15 St., Augusta, GA 30912. Tel:706-721-6897 Fax:706-721-7959 E-mail:lak{at}immag.mcg.edu.

We generated vascular cell adhesion molecule (VCAM)-1 "knock-in"mice and Cre recombinase transgenic mice to delete the VCAM-1gene (vcam-1) in whole mice, thereby overcoming the embryoniclethality seen with conventional vcam-1–deficient mice.vcam-1 knock-in mice expressed normal levels of VCAM-1 but showedloss of VCAM-1 on endothelial and hematopoietic cells when interbredwith a "TIE2Cre" transgene. Analysis of peripheral blood fromconditional vcam-1–deficient mice revealed mild leukocytosis,including elevated immature B cell numbers. Conversely, thebone marrow (BM) had reduced immature B cell numbers, but normalnumbers of pro-B cells. vcam-1–deficient mice also hadreduced mature IgD⁺ B and T cells in BM and a greatly reducedcapacity to support short-term migration of transferred B cells,CD4⁺ T cells, CD8⁺ T cells, and preactivated CD4⁺ T cells tothe BM. Thus, we report an until now unappreciated dominantrole for VCAM-1 in lymphocyte homing to BM.

Key Words: VCAM-1, Cre recombinase, knockout mice, bone marrow, lymphocytemigration

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