Conditional vascular cell adhesion molecule 1 deletion in mice: impaired lymphocyte migration to bone marrow.
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.
Molecular Immunology Program, Institute of Molecular Medicine and Genetics, Medical College of Georgia, 1120 15 St., Room CA2007, Augusta, GA 30912, USA. lak@immag.mcg.edu
P A
PA
Koni
S K
SK
Joshi
U A
UA
Temann
D
D
Olson
L
L
Burkly
R A
RA
Flavell
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001853:Bone Marrow / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*
D019010:Vascular Cell Adhesion Molecule-1