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Abstract

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.

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First Claim