Multicellular living organisms and unmodified parts thereof and – Nonhuman animal
Patent
1995-02-21
1998-03-24
Rories, Charles C. P.
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
800DIG1, 800DIG3, 800DIG4, 4351723, 435375, C12N 1500, C12N 1587, C12N 1590, C12N 510
Patent
active
057314900
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.
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Mak Tak W.
Taniguchi Tadatsugu
Rories Charles C. P.
The Ontario Cancer Institute
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