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Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development.

Cell | Oct 8, 1993

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.

Pubmed ID: 8402903 RIS Download

Mesh terms: Animals | Antibody Formation | B-Lymphocytes | Base Sequence | Bone Marrow | Chimera | DNA Primers | DNA-Binding Proteins | Embryo, Mammalian | Gene Expression | Gene Expression Regulation | Hematopoiesis | Interferon Regulatory Factor-1 | Interferon Regulatory Factor-2 | Interferon Type I | Lymphocytes | Mice | Mice, Inbred BALB C | Mice, Inbred C57BL | Mice, Inbred DBA | Molecular Sequence Data | Multigene Family | Newcastle disease virus | Phosphoproteins | Polymerase Chain Reaction | RNA, Messenger | Repressor Proteins | Stem Cells | T-Lymphocyte Subsets | T-Lymphocytes | Transcription Factors | Transcriptional Activation | Vesicular stomatitis Indiana virus

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Associated grants


Mouse Genome Informatics (Data, Gene Annotation)

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