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

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

Authors

  • Matsuyama T
  • Kimura T
  • Kitagawa M
  • Pfeffer K
  • Kawakami T
  • Watanabe N
  • K√ľndig TM
  • Amakawa R
  • Kishihara K
  • Wakeham A

Journal

Cell

Publication Data

October 8, 1993

Associated Grants

None

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