Rapid conditional targeted ablation of cells expressing human CD59 in transgenic mice by intermedilysin

Weiguo Hu, Sean P. Ferris, Rodney K. Tweten, Gongxiong Wu, Svetlana Radaeva, Bin Gao, Roderick T. Bronson, Jose A. Halperin, Xuebin Qin

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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 ThCD59RBC) or on endothelia (strain ThCD59END). Intravenous injection of ILY in ThCD59RBC mice induced acute intravascular hemolysis, leading to reduced nitric oxide bioavailability, increased platelet activation and rapid death. In ThCD59END 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.

Original languageEnglish
Pages (from-to)98-103
Number of pages6
JournalNature Medicine
Volume14
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

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