A novel Ncr1-Cre mouse reveals the essential role of STAT5 for NK-cell survival and development

Abstract

Abstract 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 Stat5f/fNcr1-iCreTg animals. Stat5f/fNcr1-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.