title: Creation and characterization of E-selectin- and VCAM-1-deficient mice.
abstract: A variety of adhesion molecules have been identified which mediate the interaction of leukocytes with endothelial cells. In order to define the role of individual molecules in inflammation we have produced lines of mice which are deficient in the synthesis of specific adhesion molecules. Null mutations were introduced into the genes encoding E-selectin or vascular cell adhesion molecule-1 (VCAM-1) in embryonic stem cells and these cells were used to produce lines of mice carrying the mutation. E-selectin-deficient mice were viable and exhibited no developmental defects. The roles of E- and P-selectin in the influx of neutrophils were examined using these mice. The data suggest that the two selectins are functionally redundant in mediating neutrophil emigration in a model of chemically induced peritonitis. VCAM-1-deficient mice are not viable. Analysis of VCAM-1 gene expression in wild-type embryos and phenotypic analysis of VCAM-1 -/- embryos suggests that VCAM-1 is required for development of the extraembryonic circulatory system and the embryonic heart.
authors.affiliation: Roche Research Center, Department of Biotechnology, Hoffman-La Roche Inc., Nutley, NJ 07110-1199, USA.
authors.forename: L
authors.initials: L
authors.lastname: Kwee
authors.forename: D K
authors.initials: DK
authors.lastname: Burns
authors.forename: J M
authors.initials: JM
authors.lastname: Rumberger
authors.forename: C
authors.initials: C
authors.lastname: Norton
authors.forename: B
authors.initials: B
authors.lastname: Wolitzky
authors.forename: R
authors.initials: R
authors.lastname: Terry
authors.forename: K M
authors.initials: KM
authors.lastname: Lombard-Gillooly
authors.forename: D J
authors.initials: DJ
authors.lastname: Shuster
authors.forename: F
authors.initials: F
authors.lastname: Kontgen
authors.forename: C
authors.initials: C
authors.lastname: Stewart
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D019040:E-Selectin / Q000502:physiology*; D005314:Embryonic and Fetal Development; D051379:Mice; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology*
chemical_list: D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1