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Mouse Model

Impaired myelopoiesis in mice devoid of interferon regulatory factor 1

Leukemia volume 18, pages 1864–1871 (2004)Cite this article

Abstract

Interferon regulatory factor (IRF)-1 is a transcription factor controlling the expression of several genes, which are differentially induced depending on the cell type and signal. IRF-1 modulates multiple functions, including regulation of immune responses and host defence, cell growth, cytokine signalling and hematopoietic development. Here, we investigated the role of IRF-1 in granulocytic differentiation in mice with a null mutation in the IRF-1 gene. We show that IRF-1−/− bone marrow cells exhibit an increased number of immature granulocytic precursors, associated with a decreased number of mature granulocytic elements as compared to normal mice, suggestive of a defective maturation process. Clonogenetic analyses revealed a reduced number of CFU-G, CFU-M and CFU-GM colonies in IRF-1−/− mice, while the number of BFU-E/CFU-E colonies was unchanged. At the molecular level, the expression of CAAT-enhancer-binding protein (C/EBP)-ɛ, -α and PU.1 was substantially lower in the CD11b+ cells from the bone marrow of IRF-1−/− mice as compared to cells from wild-type mice. These results, together with the fact that IRF-1 is markedly induced early during granulo-monocytic differentiation of CD34+ cells, highlight the pivotal role of IRF-1 in the early phases of myelopoiesis.

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Acknowledgements

We thank Sabrina Tocchio for secretarial and editorial assistance and Roberto Gilardi for preparing graphs. This work was partially supported by Institutional grants from the Istituto Superiore di Sanità, 1% Projects, and Special Project on AIDS to AB.

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Authors and Affiliations

  1. Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy

    U Testa, E Pelosi, E Petrucci & L Pasquini

  2. Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy

    E Stellacci, R Orsatti, A Fragale & A Battistini

  3. Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy

    P Sestili, M Venditti, F Belardelli & L Gabriele

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  1. U Testa
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Correspondence to A Battistini.

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Testa, U., Stellacci, E., Pelosi, E. et al. Impaired myelopoiesis in mice devoid of interferon regulatory factor 1. Leukemia 18, 1864–1871 (2004). https://doi.org/10.1038/sj.leu.2403472

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