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Stem Cell Related Patent Number US5731490

Title:Mutant mouse lacking the expression of interferon regulatory factor 1 (IRF-1)
Inventors:Mak, Tak W.; Toronto, Canada
Taniguchi, Tadatsugu; Osaka, Japan
Summary:This invention is a type of mouse, in which the Interferon Regulatory Factor-1 (IRF-1) genes of the mouse have been disrupted at the embryonic stage, thereby preventing the synthesis of functional IRF-1 cells. The result is a mutant mouse having a reduced number of CD4- 8+ T cells in comparison to the number of CD4- 8+ T cells in a mouse without the disrupted IRF-1 genes.
Abstract: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-.beta.. 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.alpha..beta..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.
US Patent Website:Click Here for Full Text of Patent
Title Number:US5731490
Application Number:US1995000392292
Date Filed:21/02/1995
Date Published:24/03/1998
Assignee:The Ontario Cancer Institute, Toronto, Canada

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