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Blood, 1 September 2004, Vol. 104, No. 5, pp. 1306-1313. Prepublished online as a Blood First Edition Paper on May 11, 2004; DOI 10.1182/blood-2004-04-1522. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1522v1 104/5/1306    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Antonchuk, J. Articles by Alexander, W. S. Search for Related Content PubMed PubMed Citation Articles by Antonchuk, J. Articles by Alexander, W. S. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Synergistic effects on erythropoiesis, thrombopoiesis, and stem cell competitiveness in mice deficient in thrombopoietin and steel factor receptors Jennifer Antonchuk, Craig D. Hyland, Douglas J. Hilton, and Warren S. Alexander From the Cancer & Haematology Division, the Walter & Eliza Hall Institute of Medical Research, Parkville, Australia. The degree of redundancy between thrombopoietin (Tpo) and steel factor (SF) cytokine pathways in the regulation of hematopoiesis was investigated by generating mice lacking both c-Mpl and fully functional c-Kit receptors. Double-mutant c-Mpl–/–KitWv/Wv mice exhibited reduced viability, making up only 2% of the offspring from c-Mpl–/–KitWv/+ intercrosses. The thrombocytopenia and megakaryocytopenia characteristic of c-Mpl–/– mice was unchanged in c-Mpl–/–KitWv/Wv mice. However, the number of megakaryocytic colony forming units (CFU-Mks) was significantly reduced, particularly in the spleen. While KitWv/Wv mice, but not c-Mpl–/– mice, are anemic, the anemia was more severe in double-mutant c-Mpl–/–KitWv/Wv mice, indicating redundancy between Tpo and SF in erythropoiesis. At the primitive cell level, c-Mpl–/– and KitWv/Wv mice have similar phenotypes, including reduced progenitors, colony forming units–spleen (CFU-Ss), and repopulating activities. All of these parameters were exacerbated in double-mutant mice. c-Mpl–/–KitWv/Wv mice had 8-fold fewer clonogenic progenitor cells and at least 28-fold fewer CFU-Ss. c-Mpl–/– mice also demonstrated a reduced threshold requirement for nonmyeloablative transplant repopulation, a trait previously associated only with KitW mice, and the level of nonmyeloablative engraftment was significantly greater in c-Mpl–/– KitWv/Wv double mutants. Thus, c-Mpl–/– KitWv/Wv mice reveal nonredundant and synergistic effects of Tpo and SF on primitive hematopoietic cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. J. Lannutti, A. Epp, J. Roy, J. Chen, and N. C. Josephson Incomplete restoration of Mpl expression in the mpl-/- mouse produces partial correction of the stem cell-repopulating defect and paradoxical thrombocytosis Blood, February 19, 2009; 113(8): 1778 - 1785. [Abstract] [Full Text] [PDF] J. L. Abkowitz and J. Chen Studies of c-Mpl function distinguish the replication of hematopoietic stem cells from the expansion of differentiating clones Blood, June 15, 2007; 109(12): 5186 - 5190. [Abstract] [Full Text] [PDF] A. Zeuner, M. Signore, D. Martinetti, M. Bartucci, C. Peschle, and R. De Maria Chemotherapy-Induced Thrombocytopenia Derives from the Selective Death of Megakaryocyte Progenitors and Can Be Rescued by Stem Cell Factor Cancer Res., May 15, 2007; 67(10): 4767 - 4773. [Abstract] [Full Text] [PDF] T. Katsumoto, Y. Aikawa, A. Iwama, S. Ueda, H. Ichikawa, T. Ochiya, and I. Kitabayashi MOZ is essential for maintenance of hematopoietic stem cells. Genes & Dev., May 15, 2006; 20(10): 1321 - 1330. [Abstract] [Full Text] [PDF] A. L. Smith, F. M. Ellison, J. P. McCoy Jr., and J. Chen c-Kit Expression and Stem Cell Factor-Induced Hematopoietic Cell Proliferation Are Up-Regulated in Aged B6D2F1 Mice J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2005; 60(4): 448 - 456. [Abstract] [Full Text] [PDF]

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