Mutant mouse lacking the expression of interferon regulatory factor 1 (IRF-1)

摘要

Interferon regulatory factor-1 (IRF-1) is implicated in the regulation of type I interferons (IFN) and cell growth. The invention is a mutant mouse lacking expression of the IRF-1 gene. Mice lacking IRF-1 did not differ from normal mice in size, behaviour, or reproductive ability. With fibroblasts derived from these mutant mice, it was shown that type I IFN induction is dramatically reduced when cells are induced by poly(I) :poly(C). In contrast, no differences were found when cells are induced by New Castle Disease Virus (NDV), or induced by poly(I) :poly(C) with prior treatment of IFN-&bgr;. On the other hand, the induction levels of IFN-inducible genes such as MHC class I and 2'-5' oligoadenylate synthetase (2'5'OAS) were not affected. Collectively, these results illustrate an IRF-1 independent mechanism of gene induction for type I IFN and these IFN-inducible genes. The critical role of IRF-1 in the immune system has been documented for the first time by the observation that the number of TcR&agr;&bgr;.sup.+ CD4.sup.- CD8.sup.+ T cells were dramatically reduced in IRF-1 deficient mice. This phenotype may be ascribed to a thymocyte developmental defect between the double positive and single positive stages during CD8.sup.+ T cell ontogeny.