First Author | Testa U | Year | 2004 |
Journal | Leukemia | Volume | 18 |
Issue | 11 | Pages | 1864-71 |
PubMed ID | 15385939 | Mgi Jnum | J:94400 |
Mgi Id | MGI:3512706 | Doi | 10.1038/sj.leu.2403472 |
Citation | Testa U, et al. (2004) Impaired myelopoiesis in mice devoid of interferon regulatory factor 1. Leukemia 18(11):1864-71 |
abstractText | 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)-epsilon, -alpha 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. |