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Blood, 15 July 2006, Vol. 108, No. 2, pp. 726-733.
Prepublished online as a Blood First Edition Paper on March 14, 2006; DOI 10.1182/blood-2005-10-4064.
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RED CELLS
Real-time monitoring of stress erythropoiesis in vivo using Gata1 and -globin LCR luciferase transgenic mice
Mikiko Suzuki,
Kinuko Ohneda,
Sakie Hosoya-Ohmura,
Saho Tsukamoto,
Osamu Ohneda,
Sjaak Philipsen, and
Masayuki Yamamoto
From the Graduate School of Comprehensive Human Sciences, the Center for Tsukuba Advanced Research Alliance (TARA), and the Environmental Response Project, Exploratory Research for Advanced Technology, Japan Science and Technology Corporation, University of Tsukuba, Japan; and the Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands.
Erythroid progenitors have the potential to proliferate rapidly in response to environmental stimuli. This process is referred to as stress erythropoiesis, with erythropoietin (EPO) playing central roles in its promotion. In this study, we wanted to elucidate the molecular mechanisms governing the regulation of stress erythropoiesis and the maintenance of red-cell homeostasis. This was achieved by our development of a noninvasive real-time monitoring system for erythropoiesis using transgenic mouse lines expressing luciferase under the control of the mouse Gata1 hematopoietic regulatory domain (G1-HRD-luc) or human -globin locus control region (Hbb-LCR-luc). Optical bioluminescence images revealed that the luciferase was specifically expressed in spleen and bone marrow and was induced rapidly in response to anemia and hypoxia stimuli. The G1-HRD-luc activity tracked the emergence and disappearance of proerythroblast-stage progenitors, whereas the Hbb-LCR-luc activity tracked erythroblasts and later stage erythroid cells. Increased plasma EPO concentration preceded an increase in G1-HRD-luc, supporting our contention that EPO acts as the key upstream signal in stress erythropoiesis. Hence, we conclude that G1-HRD-luc and Hbb-LCR-luc reporters are differentially activated during stress erythropoiesis and that the transgenic mouse lines used serve as an important means for understanding the homeostatic regulation of erythropoiesis.

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