SEARCH:   Advanced

Blood, 1 June 2004, Vol. 103, No. 11, pp. 4126-4133. Prepublished online as a Blood First Edition Paper on February 12, 2004; DOI 10.1182/blood-2003-10-3557. This Article Full Text (PDF) All Versions of this Article: 2003-10-3557v1 103/11/4126    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Brun, A. C Articles by Karlsson, S. Search for Related Content PubMed PubMed Citation Articles by Brun, A. C Articles by Karlsson, S. Social Bookmarking                   What's this? Submitted October 20, 2003 Accepted February 4, 2004 Hoxb4 deficient mice have normal hematopoietic development but exhibit a mild proliferation defect in hematopoietic stem cells Ann C Brun*, Jon Mar Bjornsson, Mattias Magnusson, Nina Larsson, Per Leveen, Mats Ehinger, Eva Nilsson, and Stefan Karlsson Department of Molecular Medicine & Gene Therapy, Lund University Hospital, Lund, Sweden; Lund Strategic Center for Stem Cell Biology and Cell Therapy, Lund University Hospital, Lund, Sweden Department of Pathology, Lund University Hospital, Lund, Sweden * Corresponding author; email: Ann.Brun{at}molmed.lu.se. Enforced expression of Hoxb4 dramatically increases the regeneration of murine hematopoietic stem cells (HSC) following transplantation, and enhances repopulation ability of human SCID repopulating cells. Therefore, we asked what physiological role Hoxb4 has in hematopoiesis. A novel mouse model lacking the entire Hoxb4 gene exhibits significantly reduced cellularity in spleen and bone marrow (BM) and a subtle reduction in red blood cell counts and hemoglobin values. A mild reduction was observed in the numbers of primitive progenitors and stem cells in both adult BM and fetal liver (FL), while lineage distribution was normal. Although cell cycle kinetics of primitive progenitors was normal during endogenous hematopoiesis, defects in proliferative responses of BM Lin- Sca1+ c-kit+ stem and progenitor cells were observed in culture, and in vivo following transplantation of BM and FL HSC. Quantitative analysis of mRNA from FL revealed that deficiency of Hoxb4 alone changed the expression levels of several other Hox genes as well as genes involved in cell cycle regulation. In summary, deficiency of Hoxb4 leads to hypocellularity in hematopoietic organs and impaired proliferative capacity. However, Hoxb4 is not required for generation of HSC or maintenance of steady state hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. E. Purton, S. Dworkin, G. H. Olsen, C. R. Walkley, S. A. Fabb, S. J. Collins, and P. Chambon RAR{gamma} is critical for maintaining a balance between hematopoietic stem cell self-renewal and differentiation J. Exp. Med., May 15, 2006; 203(5): 1283 - 1293. [Abstract] [Full Text] [PDF] H. J. Lawrence, J. Christensen, S. Fong, Y.-L. Hu, I. Weissman, G. Sauvageau, R. K. Humphries, and C. Largman Loss of expression of the Hoxa-9 homeobox gene impairs the proliferation and repopulating ability of hematopoietic stem cells Blood, December 1, 2005; 106(12): 3988 - 3994. [Abstract] [Full Text] [PDF] H. Hock, E. Meade, S. Medeiros, J. W. Schindler, P. J.M. Valk, Y. Fujiwara, and S. H. Orkin Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival Genes & Dev., October 1, 2004; 18(19): 2336 - 2341. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020