Abstract
BackgroundHuman CEACAM1 is a cell-cell adhesion molecule with multiple functions including insulin clearance in the liver, vasculogenesis in endothelial cells, lumen formation in the mammary gland, and binding of certain human pathogens.Principal FindingsThree genomic BAC clones containing the human CEACAM1 gene were microinjected into pronuclei of fertilized FVB mouse oocytes. The embryos were implanted in the oviducts of pseudopregnant females and allowed to develop to term. DNA from newborn mice was evaluated by PCR for the presence of the human CEACAM1 gene. Feces of the PCR positive offspring screened for expression of human CEACAM1. Using this assay, one out of five PCR positive lines was positive for human CEACAM1 expression and showed stable transmission to the F1 generation with the expected transmission frequency (0.5) for heterozygotes. Liver, lung, intestine, kidney, mammary gland, and prostate were strongly positive for the dual expression of both murine and human CEACAM1 and mimic that seen in human tissue. Peripheral blood and bone marrow granulocytes stained strongly for human CEACAM1 and bound Neisseria Opa proteins similar to that in human neutrophils.ConclusionThese transgenic animals may serve as a model for the binding of human pathogens to human CEACAM1.
Highlights
CEACAM1 is a type 1 transmembrane protein expressed on most epithelial cells, phagocytes and activated lymphocytes [1,2]
These transgenic animals may serve as a model for the binding of human pathogens to human CEACAM1
Generation of human CEACAM1 transgenic mice Three Bacterial Artificial Chromosome (BAC) clones containing the human CEACAM1 gene were microinjected into the pronuclei of fertilized oocytes of FVB N/J
Summary
CEACAM1 (carcinoembryonic antigen related cell adhesion molecule-1) is a type 1 transmembrane protein expressed on most epithelial cells, phagocytes and activated lymphocytes [1,2]. In the case of epithelial cells, its cell adhesion activity is associated with diverse functions including angiogenesis [3,4], lumen formation [5,6,7] and the binding of extracellular pathogens [8]. In the case of neutrophils, it may play a role in the binding of neutrophils to activated endothelium and extravasation into inflamed tissues [9,10], and similar to epithelial cells, may bind extracellular pathogens [8,11,12]. CEACAM1 is a critical molecule well situated to play a communication role between epithelial cells, that represent the first barrier to infection, and immune cells that control infections that disrupt the epithelial barrier. Human CEACAM1 is a cell-cell adhesion molecule with multiple functions including insulin clearance in the liver, vasculogenesis in endothelial cells, lumen formation in the mammary gland, and binding of certain human pathogens
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