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Blood, 15 October 2007, Vol. 110, No. 8, pp. 3049-3055. Prepublished online as a Blood First Edition Paper on July 16, 2007; DOI 10.1182/blood-2007-02-074393. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-02-074393v1 110/8/3049    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pan, D. Articles by Skoda, R. C. Search for Related Content PubMed PubMed Citation Articles by Pan, D. Articles by Skoda, R. C. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Red Cells Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Normal erythropoiesis but severe polyposis and bleeding anemia in Smad4-deficient mice Dejing Pan1, Tibor Schomber1, Christian P. Kalberer1, Luigi M. Terracciano2, Katrin Hafen3, Werner Krenger3, Hui Hao-Shen1, Chuxia Deng4, and Radek C. Skoda1 1 Department of Research, Experimental Hematology, University Hospital Basel, Basel, Switzerland; 2 Department of Pathology, University Hospital Basel, Basel, Switzerland, and Department of Health Sciences, University of Molise, Campobasso, Italy; 3 Department of Clinical-Biological Sciences, Laboratory of Pediatric Immunology, University of Basel and Basel University Children's Hospital (UKBB), Basel, Switzerland; 4 Mammalian Genetics Section, Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD The tumor suppressor Smad4 mediates signaling by the transforming growth factor beta (TGF-ß) superfamily of ligands. Previous studies showed that several TGF-ß family members exert important functions in hematopoiesis. Here, we studied the role of Smad4 in adult murine hematopoiesis using the inducible Mx-Cre/loxP system. Mice with homozygous Smad4 deletion (Smad4/) developed severe anemia 6 to 8 weeks after induction (mean hemoglobin level 70 g/L). The anemia was not transplantable, as wild-type mice reconstituted with Smad4/ bone marrow cells had normal peripheral blood counts. These mice did not develop an inflammatory disease typical for mice deficient in TGF-ß receptors I and II, suggesting that the suppression of inflammation by TGF-ß is Smad4 independent. The same results were obtained when Smad4 alleles were deleted selectively in hematopoietic cells using the VavCre transgenic mice. In contrast, lethally irradiated Smad4/ mice that received wild-type bone marrow cells developed anemia similar to Smad4/ mice that did not receive a transplant. Liver iron stores were decreased and blood was present in stool, indicating that the anemia was due to blood loss. Multiple polyps in stomach and colon represent a likely source of the bleeding. We conclude that Smad4 is not required for adult erythropoiesis and that anemia is solely the consequence of blood loss. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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