VCAM-1 ablation in nonhematopoietic cells in MxCre + VCAM-1 f/f mice is variable and dictates their phenotype

Abstract

The goal of the present study was to assess the extent of vascular cell adhesion molecule-1 (VCAM-1) gene deletion in hematopoietic vs nonhematopoietic cells in the bone marrow (BM) of MxCre(+)VCAM-1(f/f) mice and its impact on the phenotypic features of these mice. VCAM-1 ablation was evaluated at the genomic level by polymerase chain reaction (PCR), at the mRNA level by real-time PCR, and at the protein level by fluorescein-activated cell sorting and immunohistochemistry. The homing or mobilization of colony-forming unit cultures was assessed by standard assays. A previously accepted interferon-induction scheme yielded efficient VCAM-1 ablation in hematopoietic cells but variable ablation in BM fibroblasts and endothelial cells. The level of ablation in the latter populations correlated with alterations in the hematopoietic phenotype. Poly(I:C)-induced MxCre-mediated gene ablation is highly efficient in hematopoietic cells but variable and partial in nonhematopoietic cells in BM. Ablation of VCAM-1 in hematopoietic cells does not contribute to their mobilization, nor does it impair their homing. The latter is dependent on VCAM-1 ablation in nonhematopoietic cells of BM.