Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins.
To examine whether globotriaosylceramide (Gb3/CD77) is a receptor for verotoxins (VTs) in vivo, sensitivity of Gb3/CD77 synthase null mutant mice to VT-2 and VT-1 was analyzed. Although wild-type mice died after administration of 0.02 microg of VT-2 or 1.0 microg of VT-1, the mutant mice showed no reaction to doses as much as 100 times that administered to wild types. Expression analysis of Gb3/CD77 in mouse tissues with antibody revealed that low, but definite, levels of Gb3/CD77 were expressed in the microvascular endothelial cells of the brain cortex and pia mater and in renal tubular capillaries. Corresponding to the Gb3/CD77 expression, tissue damage with edema, congestion, and cytopathic changes was observed, indicating that Gb3/CD77 (and its derivatives) exclusively function as a receptor for VTs in vivo. The lethal kinetics were similar regardless of lipopolysaccharide elimination in VT preparation, suggesting that basal Gb3/CD77 levels are sufficient for lethal effects of VTs.
Pubmed ID: 16476743 RIS Download
Animals | Blotting, Northern | Blotting, Southern | Brain | Chromatography, Thin Layer | Cytokines | Escherichia coli | Female | Galactosyltransferases | Gene Deletion | Gene Expression Regulation | Gene Expression Regulation, Enzymologic | Genetic Vectors | Glycolipids | Glycosphingolipids | Immunohistochemistry | Inflammation | Interleukin-1 | Kidney | Kidney Tubules | Kinetics | Lipopolysaccharides | Lymphocytes | Male | Mice | Mice, Knockout | Microcirculation | Models, Genetic | Mutation | Recombination, Genetic | Reverse Transcriptase Polymerase Chain Reaction | Shiga Toxins | Time Factors | Tumor Necrosis Factor-alpha