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Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Mice bearing a targeted interruption of the homeobox gene HOXA9 have defects in myeloid, erythroid, and lymphoid hematopoiesis HJ Lawrence, CD Helgason, G Sauvageau, S Fong, DJ Izon, RK Humphries and C Largman Department of Medicine, University of California, San Francisco 94121, USA. Several homeobox genes of the HOXA and HOXB clusters are expressed in primitive blood cells, suggesting a role for HOX genes in normal hematopoiesis. The HOXA9 gene is expressed in CD34+ marrow cells and in developing lymphocytes. We examined blood-forming organs of mice homozygous for an interrupted HOXA9 allele to determine if loss of HOX gene function is deleterious to hematopoiesis. HOXA9-/- mice have approximately 30% to 40% reductions in total leukocytes and lymphocytes (P < .001) and a blunted granulocytic response to granulocyte colony- stimulating factor (G-CSF). Homozygous mice have significantly smaller spleens and thymuses. Myeloid/erythroid and pre-B progenitors in the marrow are significantly reduced, but no significant decreases are noted in mixed colonies, day 12 colony-forming units-spleen (CFU-S), or long-term culture-initiating cells (LTC-IC), suggesting little or no perturbation in earlier progenitors. Heterozygous animals display no hematopoietic defects. The abnormalities in leukocyte production are transplantable, indicating that the defect resides in the hematopoietic cells. These studies demonstrate a physiologic role for a HOX gene in blood cell differentiation, with the greatest apparent influence of HOXA9 at the level of the committed progenitor. Volume 89, Issue 6, pp. 1922-1930, 03/15/1997 Copyright © 1997 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Wang, C. Lin, E. R. Smith, H. Guo, B. W. Sanderson, M. Wu, M. Gogol, T. Alexander, C. Seidel, L. M. Wiedemann, et al. Global Analysis of H3K4 Methylation Defines MLL Family Member Targets and Points to a Role for MLL1-Mediated H3K4 Methylation in the Regulation of Transcriptional Initiation by RNA Polymerase II Mol. Cell. Biol., November 15, 2009; 29(22): 6074 - 6085. [Abstract] [Full Text] [PDF] Y.-L. Hu, S. Fong, C. Ferrell, C. Largman, and W.-F. Shen HOXA9 Modulates Its Oncogenic Partner Meis1 To Influence Normal Hematopoiesis Mol. Cell. Biol., September 15, 2009; 29(18): 5181 - 5192. [Abstract] [Full Text] [PDF] S. R. Horman, C. S. Velu, A. Chaubey, T. Bourdeau, J. Zhu, W. E. Paul, B. Gebelein, and H. L. 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