Real-time monitoring of stress erythropoiesis in vivo using Gata1 and β-globin LCR luciferase transgenic mice

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 r...

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Bibliographic Details
Published in:Blood 2006-07, Vol.108 (2), p.726-733
Main Authors: Suzuki, Mikiko, Ohneda, Kinuko, Hosoya-Ohmura, Sakie, Tsukamoto, Saho, Ohneda, Osamu, Philipsen, Sjaak, Yamamoto, Masayuki
Format: Article
Language:English
Subjects:
Animals
Erythroid Precursor Cells - cytology
Erythropoiesis - genetics
Erythropoietin - blood
Erythropoietin - physiology
GATA1 Transcription Factor - genetics
Gene Expression Regulation
Genes, Reporter
Globins - genetics
Humans
Locus Control Region - genetics
Luciferases - genetics
Luminescence
Methods
Mice
Mice, Transgenic
Stress, Physiological - genetics
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Summary: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 β-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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2005-10-4064