TARGETED DISRUPTION OF IRF-1 OR IRF-2 RESULTS IN ABNORMAL TYPE-I IFN GENE INDUCTION AND ABERRANT LYMPHOCYTE DEVELOPMENT
TARGETED DISRUPTION OF IRF-1 OR IRF-2 RESULTS IN ABNORMAL TYPE-I IFN GENE INDUCTION AND ABERRANT LYMPHOCYTE DEVELOPMENT
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DOI：
10.1016/s0092-8674(05)80086-8
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发表时间：
1993-10-08
期刊：
影响因子：
64.5
通讯作者：
MAK, TW
中科院分区：
文献类型：
--
作者：
MATSUYAMA, T;KIMURA, T;MAK, TW
干扰素调节因子1 （IRF-1）是一种转录激活因子，其拮抗抑制因子IRF-2最初被确定为I型干扰素（IFN）系统的调节因子。我们在胚胎干细胞中通过基因靶向产生了IRF-1或IRF-2缺失的小鼠。irf -1缺陷成纤维细胞缺乏poly(I):poly(C)通常观察到的I型IFN诱导，而它们在新城疫病毒（NDV）感染后诱导I型IFN达到与野生型相似的水平。相反，irf -2缺陷成纤维细胞在NDV感染下表现出I型IFN诱导上调。在胸腺细胞发育缺陷的IRF-1缺陷小鼠中，tcrα - β +CD4-CD8+ T细胞显著减少，揭示了IRF-1在T细胞发育中的关键作用。irf -2缺陷小鼠在淋巴细胞性脉络丛脑膜炎病毒感染后表现出造血和B淋巴生成的骨髓抑制和死亡。
Interferon regulatory factor 1 (IRF-1), a transcriptional activator, and its antagonistic repressor, IRF-2, were originally identified as regulators of the type I interferon (IFN) system. We have generated mice deficient in either IRF-1 or IRF-2 by gene targeting in embryonic stem cells. IRF-1-deficient fibroblasts lacked the normally observed type I IFN induction by poly(I):poly(C), while they induced type I IFN to similar levels as the wild type following Newcastle disease virus (NDV) infection. In contrast, IRF-2-deficient fibroblasts showed up-regulated type I IFN induction by NDV infection. A profound reduction of TCRalphabeta+CD4-CD8+ T cells in IRF-1-deficient mice, with a thymocyte developmental defect, reveals a critical role for IRF-1 in T cell development. IRF-2-deficient mice exhibited bone marrow suppression of hematopoiesis and B lymphopoiesis and mortality following lymphocytic choriomeningitis virus infection.