title: Cre-inducible human CD59 mediates rapid cell ablation after intermedilysin administration.
abstract: Cell ablation is a powerful tool for studying cell lineage and/or function; however, current cell-ablation models have limitations. Intermedilysin (ILY), a cytolytic pore-forming toxin that is secreted by Streptococcus intermedius, lyses human cells exclusively by binding to the human complement regulator CD59 (hCD59), but does not react with CD59 from nonprimates. Here, we took advantage of this feature of ILY and developed a model of conditional and targeted cell ablation by generating floxed STOP-CD59 knockin mice (ihCD59), in which expression of human CD59 only occurs after Cre-mediated recombination. The administration of ILY to ihCD59+ mice crossed with various Cre-driver lines resulted in the rapid and specific ablation of immune, epithelial, or neural cells without off-target effects. ILY had a large pharmacological window, which allowed us to perform dose-dependent studies. Finally, the ILY/ihCD59-mediated cell-ablation method was tested in several disease models to study immune cell functionalities, hepatocyte and/or biliary epithelial damage and regeneration, and neural cell damage. Together, the results of this study demonstrate the utility of the ihCD59 mouse model for studying the effects of cell ablation in specific organ systems in a variety of developmental and disease states.
authors.forename: Dechun
authors.initials: D
authors.lastname: Feng
authors.forename: Shen
authors.initials: S
authors.lastname: Dai
authors.forename: Fengming
authors.initials: F
authors.lastname: Liu
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ohtake
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Alison
authors.initials: A
authors.lastname: Kearns
authors.forename: Xiao
authors.initials: X
authors.lastname: Peng
authors.forename: Faliang
authors.initials: F
authors.lastname: Zhu
authors.forename: Umar
authors.initials: U
authors.lastname: Hayat
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Mingjiang
authors.initials: M
authors.lastname: Xu
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhao
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
authors.forename: Lining
authors.initials: L
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ju
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Bryda
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gordon
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.forename: Wenhui
authors.initials: W
authors.lastname: Hu
authors.forename: Shuxin
authors.initials: S
authors.lastname: Li
authors.forename: Xuebin
authors.initials: X
authors.lastname: Qin
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001430:Bacteriocins / Q000008:administration & dosage* / Q000633:toxicity; D018957:CD59 Antigens / Q000235:genetics / Q000502:physiology*; D055879:Gene Knock-In Techniques; D006461:Hemolysis / Q000235:genetics / Q000502:physiology; D006520:Hepatitis, Animal / Q000209:etiology / Q000235:genetics / Q000276:immunology; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006801:Humans; D019426:Integrases; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D001430:Bacteriocins; D018957:CD59 Antigens; C403910:intermedilysin protein, Streptococcus intermedius; C051590:CD59 protein, human; C045073:Cre recombinase; D019426:Integrases