The Journal of Experimental Medicine
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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. Konia, Sunil K. Joshia, Ulla-Angela Temannb, Dian Olsond, Linda Burklyd, and Richard A. Flavellb,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
Rm. CA2007, Institute of Molecular Medicine and Genetics, Medical College of Georgia, 1120 15 St., Augusta, GA 30912.706-721-7959706-721-6897

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-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+ B and T cells in BM and a greatly reduced capacity to support short-term migration of transferred B cells, CD4+ T cells, CD8+ T cells, and preactivated CD4+ T cells to the BM. Thus, we report an until now unappreciated dominant role for VCAM-1 in lymphocyte homing to BM.

Key Words: VCAM-1 • Cre recombinase • knockout mice • bone marrow • lymphocyte migration

Abbreviations used in this paper: BM, bone marrow; CG, chicken {gamma}-globulin; CMFDA, 5-chloromethylfluorescein diacetate; DC, dendritic cell; EC, endothelial cell; ES, embryonic stem; FDC, follicular dendritic cell; GC, germinal center; HEV, high endothelial venule; ICAM, intercellular adhesion molecule; MLN, mesenteric LN; NP, 4-hydroxy-3-nitrophenyl; PLN, peripheral LN; PNA, peanut agglutinin; VCAM, vascular cell adhesion molecule; VLA, very late antigen.

© 2001 The Rockefeller University Press


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