Conditional vascular cell adhesion molecule 1 deletion in mice: Impaired lymphocyte migration to bone marrow

P. A. Koni, S. K. Joshi, U. A. Temann, D. Olson, L. Burkly, R. A. Flavell

Research output: Contribution to journalArticle

372 Scopus citations

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+ 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.

Original languageEnglish (US)
Pages (from-to)741-753
Number of pages13
JournalJournal of Experimental Medicine
Volume193
Issue number6
DOIs
StatePublished - Mar 19 2001

Keywords

  • Bone marrow
  • Cre recombinase
  • Knockout mice
  • Lymphocyte migration
  • VCAM-1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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