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Blood, 1 April 2004, Vol. 103, No. 7, pp. 2560-2567. Prepublished online as a Blood First Edition Paper on December 4, 2003; DOI 10.1182/blood-2003-07-2514. This Article Full Text (PDF) All Versions of this Article: 2003-07-2514v1 103/7/2560    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 Shimizu, R. Articles by Yamamoto, M. Search for Related Content PubMed PubMed Citation Articles by Shimizu, R. Articles by Yamamoto, M. Social Bookmarking                   What's this? Submitted July 28, 2003 Accepted November 26, 2003 Transgenic rescue of GATA-1-deficient mice with GATA-1 lacking a FOG-1 association site phenocopies patients with X-linked thrombocytopenia Ritsuko Shimizu, Kinuko Ohneda, James D Engel, Cecelia D Trainor, and Masayuki Yamamoto* Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan; Yamamoto Environmental Response Project, ERATO, Japan Science and Technology Corporation, University of Tsukuba, Tsukuba, Japan Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MA, USA * Corresponding author; email: masi{at}tara.tsukuba.ac.jp. Association of GATA-1 and its cofactor FOG-1 is essential for erythroid and megakaryocyte development. To assess functions of GATA-1-FOG-1 association during mouse development, we used the GATA-1 hematopoietic regulatory domain to generate transgenic mouse lines expressing a mutant GATA-1, which contains a substitution of glycine 205 for valine (V205G) that abrogates its association with FOG-1. We examined whether the transgenic expression of mutant GATA-1 rescues GATA-1 germ line mutants from embryonic lethality. In high expressor lines we observed that the GATA-1V205G rescues GATA-1-deficient mice from embryonic lethality at the expected frequency, revealing that excess GATA-1V205G can eliminate the lethal anemia due to GATA-1 deficiency. In contrast, transgene expression comparable to the endogenous GATA-1 level resulted in much lower frequency of rescue, indicating that the GATA-1-FOG-1 association is critical for normal embryonic hematopoiesis. Rescued mice in these analyses exhibit thrombocytopenia and display dysregulated proliferation and impaired cytoplasmic maturation of megakaryocytes. Although anemia is not observed under steady-state condition, stress erythropoiesis is attenuated in the rescued mice. Our findings reveal an indispensable role for the association of GATA-1 and FOG-1 during late stage megakaryopoiesis, and provide a unique model for X-linked thrombocytopenia with inherited GATA-1 mutation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Gutierrez, S. Tsukamoto, M. Suzuki, H. Yamamoto-Mukai, M. Yamamoto, S. Philipsen, and K. Ohneda Ablation of Gata1 in adult mice results in aplastic crisis, revealing its essential role in steady-state and stress erythropoiesis Blood, April 15, 2008; 111(8): 4375 - 4385. [Abstract] [Full Text] [PDF] D. Sugiyama, M. Tanaka, K. Kitajima, J. Zheng, H. Yen, T. Murotani, A. Yamatodani, and T. Nakano Differential context-dependent effects of friend of GATA-1 (FOG-1) on mast-cell development and differentiation Blood, February 15, 2008; 111(4): 1924 - 1932. [Abstract] [Full Text] [PDF] A. T. Nurden and P. Nurden Inherited thrombocytopenias Haematologica, September 1, 2007; 92(9): 1158 - 1164. [Full Text] [PDF] A. G. Muntean, L. Pang, M. Poncz, S. F. Dowdy, G. A. Blobel, and J. D. Crispino Cyclin D-Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization Blood, June 15, 2007; 109(12): 5199 - 5207. [Abstract] [Full Text] [PDF] R. Shimizu, C. D. Trainor, K. Nishikawa, M. Kobayashi, K. Ohneda, and M. Yamamoto GATA-1 Self-association Controls Erythroid Development in Vivo J. Biol. Chem., May 25, 2007; 282(21): 15862 - 15871. [Abstract] [Full Text] [PDF] K. Maeda, C. Nishiyama, T. Tokura, H. Nakano, S. Kanada, M. Nishiyama, K. Okumura, and H. Ogawa FOG-1 represses GATA-1-dependent Fc{epsilon}RI beta-chain transcription: transcriptional mechanism of mast-cell-specific gene expression in mice Blood, July 1, 2006; 108(1): 262 - 269. [Abstract] [Full Text] [PDF] O. Nakajima, S. Okano, H. Harada, T. Kusaka, X. Gao, T. Hosoya, N. Suzuki, S. Takahashi, and M. Yamamoto Transgenic rescue of erythroid 5-aminolevulinate synthase-deficient mice results in the formation of ring sideroblasts and siderocytes Genes Cells, June 1, 2006; 11(6): 685 - 700. [Abstract] [Full Text] [PDF] A. G. Muntean and J. D. Crispino Differential requirements for the activation domain and FOG-interaction surface of GATA-1 in megakaryocyte gene expression and development Blood, August 15, 2005; 106(4): 1223 - 1231. [Abstract] [Full Text] [PDF] K. M. Ruppel, D. Willison, H. Kataoka, A. Wang, Y.-W. Zheng, I. Cornelissen, L. Yin, S. M. Xu, and S. R. Coughlin Essential role for G{alpha}13 in endothelial cells during embryonic development PNAS, June 7, 2005; 102(23): 8281 - 8286. [Abstract] [Full Text] [PDF] M. Nakano, K. Ohneda, H. Yamamoto-Mukai, R. Shimizu, O. Ohneda, S. Ohmura, M. Suzuki, S. Tsukamoto, T. Yanagawa, H. Yoshida, et al. Transgenic over-expression of GATA-1 mutant lacking N-finger domain causes hemolytic syndrome in mouse erythroid cells Genes Cells, January 1, 2005; 10(1): 47 - 62. [Abstract] [Full Text] [PDF]

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