Matsuyama T, Kimura T, Kitagawa M, Pfeffer K, Kawakami T, Watanabe N, Kündig T M, Amakawa R, Kishihara K, Wakeham A
Amgen Institute, University of Toronto, Ontario, Canada.
Cell. 1993 Oct 8;75(1):83-97.
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 TCR alpha beta+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.
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最初被鉴定为I型干扰素（IFN）系统的调节因子。我们通过对胚胎干细胞进行基因靶向操作，培育出了IRF-1或IRF-2基因缺失的小鼠。IRF-1基因缺失的成纤维细胞在受到聚肌苷酸：聚胞苷酸（poly(I):poly(C)）刺激时，缺乏正常情况下所观察到的I型干扰素诱导现象，而在感染新城疫病毒（NDV）后，它们诱导产生I型干扰素的水平与野生型相似。相反，IRF-2基因缺失的成纤维细胞在感染NDV后，I型干扰素诱导水平上调。IRF-1基因缺失的小鼠中，TCRαβ⁺CD4⁻CD8⁺T细胞显著减少，伴有胸腺细胞发育缺陷，这揭示了IRF-1在T细胞发育中的关键作用。IRF-2基因缺失的小鼠在感染淋巴细胞性脉络丛脑膜炎病毒后，出现骨髓造血和B淋巴细胞生成抑制以及死亡现象。
