Deficient T cell fate specification in mice with an induced inactivation of Notch1
Deficient T cell fate specification in mice with an induced inactivation of Notch1
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DOI：
10.1016/s1074-7613(00)80054-0
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发表时间：
1999-05-01
期刊：
影响因子：
32.4
通讯作者：
Aguet, M
中科院分区：
文献类型：
--
作者：
Radtke, F;Wilson, A;Aguet, M
Notch蛋白是细胞表面受体，介导发育中的细胞特异性事件。为了探索小鼠Notch1的功能，将该基因的一个重要部分与loxP位点相连，并通过干扰素调节的Cre重组酶诱导其失活。新生儿诱导的Notch1功能缺失小鼠会出现短暂的生长迟缓，胸腺细胞发育严重不足。用野生型和notch -1缺陷骨髓对受致死性照射的野生型宿主进行竞争性再种群研究发现，在表达T细胞谱系标记物之前，T细胞发育的早期阶段存在细胞自主阻断。然而，缺notch - 1的骨髓确实对所有其他造血谱系都有正常贡献。这些发现表明Notch1在T细胞谱系诱导中起着强制性和选择性的作用。
Notch proteins are cell surface receptors that mediate developmental cell specification events. To explore the function of murine Notch1, an essential portion of the gene was flanked with loxP sites and inactivation induced via interferon-regulated Cre recombinase. Mice with a neonatally induced loss of Notch1 function were transiently growth retarded and had a severe deficiency in thymocyte development. Competitive repopulation of lethally irradiated wild-type hosts with wild-type- and Notch-1-deficient bone marrow revealed a cell autonomous blockage in T cell development at an early stage, before expression of T cell lineage markers. Notch1-deficient bone marrow did, however, contribute normally to all other hematopoietic lineages. These findings suggest that Notch1 plays an obligatory and selective role in T cell lineage induction.