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US 5,675,059 AGranted
Mouse lacking the expression of interferon regulatory factor 2 (IRF-2)
AssigneeThe Ontario Cancer Institute
InventorsTak W. Mak, Tadatsugu Taniguchi
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AssigneeThe Ontario Cancer Institute
InventorsTak W. Mak, Tadatsugu Taniguchi
Estimating the term…
The transcription factors, IRF-1 and IRF-2 are induced by interferons (IFNs) and a variety of other cytokines. IRF-1 functions as an activator whereas IRF-2 represses IRF-1 action by competing for binding to the same cis-elements. Recently, it has been shown that balanced expression between these two factors is critical for maintaining normal restraints on cell growth. Mutant mice deficient for IRF-2 were prepared by homologous recombination. In mutant cells, infection by Newcastle disease virus (NDV) resulted in the induction of type I IFN (IFN-.alpha. and IFN-.beta.) mRNAs, the levels of which were significantly higher than in wild type cells; whereas, such a difference was not found upon induction by poly(I):poly(C). Unlike the IRF-1 deficient mutant mice, the IRF-2 deficient mice of the invention exhibit multiple phenotypes of physical vulnerability, including lethality to lymphocytic choriomeningitis virus (LCMV). Furthermore, in vitro colony formation assays have revealed a remarkable suppression of B cell lymphopoiesis in IRF-2 deficient mice.
A mutant mouse comprising disrupted alleles of the Interferon Regulatory Factor-2 (IRF-2) gene, the disruption being introduced into the mouse or an ancestor of the mouse at an embryonic stage, wherein the disruption prevents the synthesis of functional IRF-2 in cells of the mouse and results in the mutant mouse having an increased susceptibility to infection by lymphocytic choriomeningitis virus (LCMV) relative to the LCMV susceptibility of a mouse comprising an undisrupted IRF-2 gene.
An embryonic stem cell line comprising a disrupted IRF-2 gene and having ATCC Accession No. CRL 11383.
A mutant mouse comprising disrupted alleles of the IRF-2 gene, the disruption being introduced into the mouse or an ancestor of the mouse at an embryonic stage using an embryonic stem cell line having ATCC Accession No. CRL 11383, wherein the disruption prevents the synthesis of functional IRF-2 in cells of the mouse and results in the mutant mouse having an increased susceptibility to infection by LCMV relative to the LCMV susceptibility of a mouse comprising an undisrupted IRF-2 gene.
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