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Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene.

Interferon consensus sequence binding protein (ICSBP) is a transcription factor of the interferon (IFN) regulatory factor (IRF) family. Mice with a null mutation of ICSBP exhibit two prominent phenotypes related to previously described activities of the IRF family. The first is enhanced susceptibility to virus infections associated with impaired production of IFN(gamma). The second is deregulated hematopoiesis in both ICSBP-/- and ICSBP+/- mice that manifests as a syndrome similar to human chronic myelogenous leukemia. The chronic period of the disease progresses to a fatal blast crisis characterized by a clonal expansion of undifferentiated cells. Normal mice injected with cells from mice in blast crisis developed acute leukemia within 6 weeks of transfer. These results suggest a novel role for ICSBP in regulating the proliferation and differentiation of hematopoietic progenitor cells.

Pubmed ID: 8861914


  • Holtschke T
  • Löhler J
  • Kanno Y
  • Fehr T
  • Giese N
  • Rosenbauer F
  • Lou J
  • Knobeloch KP
  • Gabriele L
  • Waring JF
  • Bachmann MF
  • Zinkernagel RM
  • Morse HC
  • Ozato K
  • Horak I



Publication Data

October 18, 1996

Associated Grants


Mesh Terms

  • Animals
  • Blast Crisis
  • Carrier Proteins
  • Cytotoxicity, Immunologic
  • Gene Expression Regulation
  • Hematopoiesis
  • Immunity, Cellular
  • Immunologic Deficiency Syndromes
  • Interferon Regulatory Factors
  • Interferon-alpha
  • Interferon-beta
  • Interferons
  • Leukemia, Experimental
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Mice
  • Mice, Knockout
  • Neoplasm Transplantation
  • Repressor Proteins
  • Syndrome
  • Transcription Factors
  • Virus Diseases