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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1476-1483. Prepublished online as a Blood First Edition Paper on October 21, 2004; DOI 10.1182/blood-2004-06-2302. This Article Full Text (PDF) All Versions of this Article: 2004-06-2302v1 105/4/1476    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 Couldrey, C. Articles by Bunting, K. D Search for Related Content PubMed PubMed Citation Articles by Couldrey, C. Articles by Bunting, K. D Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 16, 2004 Accepted October 14, 2004 A STAT5 modifier locus on murine chromosome 7 modulates engraftment of hematopoietic stem cells during steady-state hematopoiesis Christine Couldrey, Heath L Bradley, and Kevin D Bunting* Hematopoiesis Department, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD, USA Hematopoiesis Department, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD, USA; Department of Anatomy and Cell Biology, The George Washington University, Washington, DC, USA; Department of Medicine, Division of Hematology/Oncology, Case Western Reserve University and Center for Stem Cell and Regenerative Medicine, Cleveland, OH, USA * Corresponding author; email: kevin.bunting{at}case.edu. Homologous disruption of STAT5a and STAT5b expression (STAT5ab-/-) in mice results in hematopoietic stem cells (HSCs) that can engraft irradiated hosts alone but are non-competitive against wild-type HSCs. To explore mechanisms for this phenotype, we crossed the STAT5 mutations onto an HW80 background congenic to the original C57BL/6 that differs in a small chromosome 7 genomic locus. C57BL/6 or HW80 background STAT5ab-/- bone marrow (BM) cells showed equal repopulating function either competitively (Bradley et al. Blood 103:2965, 2004) or non-competitively in irradiated hosts. However, one intraperitoneal injection of wild-type green fluorescent protein (GFP) transgenic BM cells into unconditioned newborn STAT5ab-/- recipients of either background was sufficient for high level donor engraftment. Furthermore, haploinsufficiency of STAT5 (STAT5ab+/-) allowed improved engraftment over wild-type recipients, indicating a dose-dependent requirement for STAT5 activation. In reciprocal experiments, STAT5ab-/- BM was transplanted into non-irradiated W/Wv hosts. In these mice, C57BL/6 STAT5ab-/- BM cells were 10-fold more defective in long-term engraftment than control wild-type BM cells and HW80 STAT5ab-/- BM cells were 5- to 10-fold more defective than C57BL/6 STAT5ab-/- BM cells. Therefore, we conclude that STAT5 plays a critical role during steady-state HSC engraftment and a chromosome 7 modifier locus regulates this activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Z. Wang, G. Li, W. Tse, and K. D. Bunting Conditional deletion of STAT5 in adult mouse hematopoietic stem cells causes loss of quiescence and permits efficient nonablative stem cell replacement Blood, May 14, 2009; 113(20): 4856 - 4865. [Abstract] [Full Text] [PDF] F. Martelli, B. Ghinassi, B. Panetta, E. Alfani, V. Gatta, A. Pancrazzi, C. Bogani, A. M. Vannucchi, F. Paoletti, G. Migliaccio, et al. Variegation of the phenotype induced by the Gata1low mutation in mice of different genetic backgrounds Blood, December 15, 2005; 106(13): 4102 - 4113. [Abstract] [Full Text] [PDF]

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