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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3538-3541. Prepublished online as a Blood First Edition Paper on January 11, 2005; DOI 10.1182/blood-2004-05-2021. This Article Full Text (PDF) All Versions of this Article: 2004-05-2021v1 105/9/3538    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 Khalaf, W. F Articles by Ingram, D. A Search for Related Content PubMed PubMed Citation Articles by Khalaf, W. F Articles by Ingram, D. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 28, 2004 Accepted December 26, 2004 K-Ras is essential for normal fetal liver erythropoiesis Waleed F Khalaf, Hilary White, Mary J Wenning, Attilio Orazi, Reuben Kapur, and David A Ingram* Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA Department of Hematology/Pathology, Indiana University School of Medicine, Indianapolis, IN, USA Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA * Corresponding author; email: dingram{at}iupui.edu. In vitro studies suggest that Ras activation is necessary for erythroid cell development. However, genetic inactivation of the Ras isoforms, H-Ras, N-Ras, and K-Ras, in mice reportedly did not affect adult or fetal erythropoiesis though K-Ras -/- embryos were anemic. Given these discrepancies, we performed a more detailed analysis of fetal erythropoiesis in K-Ras -/- embryos. Day 13.5 K-Ras -/- embryos were pale with a marked reduction of mature erythrocytes in their fetal livers. The frequency and number of both early (erythroid burst-forming unit [BFU-E]) and late erythroid progenitors (erythroid colony forming unit [CFU-E]) were reduced in K-Ras -/- fetal livers compared to wild-type controls and displayed a delay in terminal erythroid cell maturation. Further, K-Ras -/- hematopoietic progenitors had reduced proliferation in response to erythropoietin and Kit ligand compared to control cells. Thus, these studies identify K-Ras as a unique Ras isoform, which is essential for regulating fetal erythropoiesis in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. B. Campbell, S. Basu, G. Hangoc, W. Tao, and H. E. Broxmeyer Overexpression of Rheb2 enhances mouse hematopoietic progenitor cell growth while impairing stem cell repopulation Blood, October 15, 2009; 114(16): 3392 - 3401. [Abstract] [Full Text] [PDF] T. S. Kendrick, C. J. Payne, M. R. Epis, J. R. Schneider, P. J. Leedman, S. P. Klinken, and E. Ingley Erythroid defects in TR{alpha}-/- mice Blood, March 15, 2008; 111(6): 3245 - 3248. [Abstract] [Full Text] [PDF] X.-S. Liu, X.-H. Li, Y. Wang, R.-Z. Shu, L. Wang, S.-Y. Lu, H. Kong, Y.-E Jin, L.-J. Zhang, J. Fei, et al. Disruption of palladin leads to defects in definitive erythropoiesis by interfering with erythroblastic island formation in mouse fetal liver Blood, August 1, 2007; 110(3): 870 - 876. [Abstract] [Full Text] [PDF] S. T. Fraser, J. Isern, and M. H. Baron Maturation and enucleation of primitive erythroblasts during mouse embryogenesis is accompanied by changes in cell-surface antigen expression Blood, January 1, 2007; 109(1): 343 - 352. [Abstract] [Full Text] [PDF] L. S. Haneline, H. White, F.-C. Yang, S. Chen, C. Orschell, R. Kapur, and D. A. Ingram Genetic reduction of class IA PI-3 kinase activity alters fetal hematopoiesis and competitive repopulating ability of hematopoietic stem cells in vivo Blood, February 15, 2006; 107(4): 1375 - 1382. [Abstract] [Full Text] [PDF] J. Zhang and H. F. Lodish Identification of K-ras as the major regulator for cytokine-dependent Akt activation in erythroid progenitors in vivo PNAS, October 11, 2005; 102(41): 14605 - 14610. [Abstract] [Full Text] [PDF]

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