Ablation of Gata1 in adult mice results in aplastic crisis, revealing its essential role in steady-state and stress erythropoiesis.
The transcription factor Gata1 is expressed in several hematopoietic lineages and plays essential roles in normal hematopoietic development during embryonic stages. The lethality of Gata1-null embryos has precluded determination of its role in adult erythropoiesis. Here we have examined the effects of Gata1 loss in adult erythropoiesis using conditional Gata1 knockout mice expressing either interferon- or tamoxifen-inducible Cre recombinase (Mx-Cre and Tx-Cre, respectively). Mx-Cre-mediated Gata1 recombination, although incomplete, resulted in maturation arrest of Gata1-null erythroid cells at the proerythroblast stage, thrombocytopenia, and excessive proliferation of megakaryocytes in the spleen. Tx-Cre-mediated Gata1 recombination resulted in depletion of the erythroid compartment in bone marrow and spleen. Formation of the early and late erythroid progenitors in bone marrow was significantly reduced in the absence of Gata1. Furthermore, on treatment with a hemolytic agent, these mice failed to activate a stress erythropoietic response, despite the rising erythropoietin levels. These results indicate that, in addition to the requirement of Gata1 in adult megakaryopoiesis, Gata1 is necessary for steady-state erythropoiesis and for erythroid expansion in response to anemia. Thus, ablation of Gata1 in adult mice results in a condition resembling aplastic crisis in human.
Gutiérrez
Laura
L
Department of Cell Biology, Erasmus Medical College, Rotterdam, The Netherlands.
Tsukamoto
Saho
S
Suzuki
Mikiko
M
Yamamoto-Mukai
Harumi
H
Yamamoto
Masayuki
M
Philipsen
Sjaak
S
Ohneda
Kinuko
K
D000741:Anemia, Aplastic / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D041905:Erythroid Cells / Q000187:drug effects / Q000473:pathology; D004920:Erythropoiesis / Q000187:drug effects; D050982:GATA1 Transcription Factor / Q000172:deficiency*; D017353:Gene Deletion; D019426:Integrases / Q000378:metabolism; D007372:Interferons / Q000494:pharmacology; D008533:Megakaryocytes / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013629:Tamoxifen / Q000494:pharmacology; D013921:Thrombocytopenia / Q000473:pathology
D050982:GATA1 Transcription Factor; D013629:Tamoxifen; D007372:Interferons; C045073:Cre recombinase; D019426:Integrases