A novel Ncr1-Cre mouse reveals the essential role of STAT5 for NK-cell survival and development
A novel Ncr1-Cre mouse reveals the essential role of STAT5 for NK-cell survival and development
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DOI：
10.1182/blood-2010-06-291633
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发表时间：
2011-02-03
期刊：
影响因子：
20.3
通讯作者：
Sexl, Veronika
中科院分区：
文献类型：
--
作者：
Eckelhart, Eva;Warsch, Wolfgang;Sexl, Veronika
我们产生了一个转基因小鼠系，表达Cre重组酶的Ncr 1（p46）启动子的控制下。Cre介导的重组严格限制于自然杀伤（NK）细胞，如通过将Ncr 1-iCreTg小鼠与eGFP-LSLTg报告菌株杂交所揭示的。通过产生Stat 5（f/f）Ncr 1-iCreTg动物，Ncr 1-iCreTg小鼠进一步用于研究Stat 5（信号转导子和转录激活子5）的NK细胞特异性功能。Stat 5（f/f）Ncr 1-iCreTg小鼠在外周淋巴器官中基本上缺乏NK细胞。在骨髓中，NK细胞成熟在NK细胞前体阶段被废除。此外，我们发现，在体外缺失Stat 5的白细胞介素2扩增的NK细胞是不相容的NK细胞的活力。体内试验证实了NK细胞介导的肿瘤控制对B16 F10黑色素瘤细胞的完全消除。相比之下，T细胞介导的肿瘤监视对MC 38-腺癌细胞是不受干扰的。总之，我们的研究结果表明，STAT 5在NK细胞发育中具有细胞内在作用，Ncr 1-iCreTg小鼠是研究NK细胞发育，生物学和功能的强大新工具。（血。2011; 117（5）：1565-1573）
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. (Blood. 2011; 117(5):1565-1573)