Abstract
Interferon regulatory factor 1 (IRF-1), a transcriptional activator, and its antagonistic repressor, IRF-2, were originally identified as regulators of the type I interferon (IFN) system. We have generated mice deficient in either IRF-1 or IRF-2 by gene targeting in embryonic stem cells. IRF-1-deficient fibroblasts lacked the normally observed type I IFN induction by poly(I):poly(C), while they induced type I IFN to similar levels as the wild type following Newcastle disease virus (NDV) infection. In contrast, IRF-2-deficient fibroblasts showed up-regulated type I IFN induction by NDV infection. A profound reduction of TCR alpha beta+CD4-CD8+ T cells in IRF-1-deficient mice, with a thymocyte developmental defect, reveals a critical role for IRF-1 in T cell development. IRF-2-deficient mice exhibited bone marrow suppression of hematopoiesis and B lymphopoiesis and mortality following lymphocytic choriomeningitis virus infection.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibody Formation
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B-Lymphocytes / immunology
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Base Sequence
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Bone Marrow / immunology
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Bone Marrow / physiology
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Chimera
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DNA Primers
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics*
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Embryo, Mammalian
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Gene Expression
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Gene Expression Regulation*
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Hematopoiesis / physiology
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Interferon Regulatory Factor-1
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Interferon Regulatory Factor-2
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Interferon Type I / biosynthesis
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Interferon Type I / genetics*
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Lymphocytes / immunology
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Lymphocytes / physiology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Inbred DBA
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Molecular Sequence Data
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Multigene Family*
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Newcastle disease virus / immunology
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Phosphoproteins / biosynthesis
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Phosphoproteins / genetics*
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Polymerase Chain Reaction
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RNA, Messenger / biosynthesis
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Repressor Proteins*
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Stem Cells / physiology
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T-Lymphocyte Subsets / immunology
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T-Lymphocytes / immunology
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Transcription Factors / biosynthesis
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Transcription Factors / genetics*
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Transcriptional Activation
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Vesicular stomatitis Indiana virus / immunology
Substances
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DNA Primers
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DNA-Binding Proteins
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Interferon Regulatory Factor-1
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Interferon Regulatory Factor-2
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Interferon Type I
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Irf1 protein, mouse
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Irf2 protein, mouse
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Phosphoproteins
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RNA, Messenger
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Repressor Proteins
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Transcription Factors