Rapid conditional targeted ablation of cells expressing human CD59 in transgenic mice by intermedilysin.
Document Type
Article
Publication Date
2008
Keywords
Antigens-CD59, Bacterial-Proteins, Bacteriocins, Endothelium, Endothelium-Vascular, Erythrocytes, Humans, Immunoglobulin-G, Mice-Transgenic, Nitric-Oxide, Recombinant-Proteins, Species-Specificity, Streptococcus-intermedius, von-Willebrand-Factor
First Page
98
Last Page
103
JAX Source
Nat Med 2008 Jan; 14(1):98-103.
Abstract
Conditional targeted cell ablation is a powerful approach for investigating the pathogenesis of human diseases and in vivo cellular functions. Intermedilysin (ILY) is a cytolytic pore-forming toxin secreted by Streptococcus intermedius that lyses human cells exclusively, owing to its receptor specificity for human CD59. We generated two transgenic mouse strains that express human CD59 either on erythrocytes (strain ThCD59(RBC)) or on endothelia (strain ThCD59(END)). Intravenous injection of ILY in ThCD59(RBC) mice induced acute intravascular hemolysis, leading to reduced nitric oxide bioavailability, increased platelet activation and rapid death. In ThCD59(END) mice, ILY induced rapid endothelial damage, leading to acute death and disseminated intravascular coagulation. Additionally, we show that human serum contains ILY-specific neutralizing antibodies not found in any other animal species. Together, these results suggest that this new rapid conditional targeted ILY-mediated cell ablation technique can be used in combination with any available transgenic expression system to study the physiologic role of specific cell populations.
Recommended Citation
Hu W,
Ferris SP,
Tweten RK,
Wu G,
Radaeva S,
Gao B,
Bronson RT,
Halperin JA,
Qin X.
Rapid conditional targeted ablation of cells expressing human CD59 in transgenic mice by intermedilysin. Nat Med 2008 Jan; 14(1):98-103.