Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development.
Journal:
Cell 1993 OctAuthors:
Matsuyama T, Kimura T, Kitagawa M, Pfeffer K, Kawakami T, Watanabe N, Kündig TM, Amakawa R, Kishihara K, Wakeham A
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) infectio
...[more]n. 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.[less]
Mesh Headings:
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