A novel Ncr1-Cre mouse reveals the essential role of STAT5 for NK-cell survival and development.
We generated a transgenic mouse line that expresses the Cre recombinase under the control of the Ncr1 (p46) promoter. Cre-mediated recombination was tightly restricted to natural killer (NK) cells, as revealed by crossing Ncr1-iCreTg mice to the eGFP-LSLTg reporter strain. Ncr1-iCreTg mice were further used to study NK cell-specific functions of Stat5 (signal transducers and activators of transcription 5) by generating Stat5(f/f) Ncr1-iCreTg animals. Stat5(f/f) Ncr1-iCreTg mice were largely devoid of NK cells in peripheral lymphoid organs. In the bone marrow, NK-cell maturation was abrogated at the NK cell-precursor stage. Moreover, we found that in vitro deletion of Stat5 in interleukin 2-expanded NK cells was incompatible with NK-cell viability. In vivo assays confirmed the complete abrogation of NK cell-mediated tumor control against B16F10-melanoma cells. In contrast, T cell-mediated tumor surveillance against MC38-adenocarcinoma cells was undisturbed. In summary, the results of our study show that STAT5 has a cell-intrinsic role in NK-cell development and that Ncr1-iCreTg mice are a powerful novel tool with which to study NK-cell development, biology, and function.
Institute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Eva
E
Eckelhart
Wolfgang
W
Warsch
Eva
E
Zebedin
Olivia
O
Simma
Dagmar
D
Stoiber
Thomas
T
Kolbe
Thomas
T
Rülicke
Mathias
M
Mueller
Emilio
E
Casanova
Veronika
V
Sexl
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000950:Antigens, Ly / Q000502:physiology*; D015153:Blotting, Western; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000502:physiology*
D000950:Antigens, Ly; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C045073:Cre recombinase; D019426:Integrases