TY - JOUR
T1 - Ablation of Gatal in adult mice results in aplastic crisis, revealing its essential role in steady-state and stress erythropoiesis
AU - Gutiérrez, Laura
AU - Tsukamoto, Saho
AU - Suzuki, Mikiko
AU - Yamamoto-Mukai, Harumi
AU - Yamamoto, Masayuki
AU - Philipsen, Sjaak
AU - Ohneda, Kinuko
PY - 2008/4/15
Y1 - 2008/4/15
N2 - The transcription factor Gatal 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 Gatal knockout mice expressing either interferon-or tamoxifen-inducible Cre re- combinase (Mx-Cre and Tx-Cre, respectively). Mx-Cre-mediated Gatal recombi-nation, 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, Gatal is necessary for steady-state erythropoiesis and for erythroid expansion in response to anemia. Thus, ablation of Gatal in adult mice results in a condition resembling aplastic crisis in human.
AB - The transcription factor Gatal 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 Gatal knockout mice expressing either interferon-or tamoxifen-inducible Cre re- combinase (Mx-Cre and Tx-Cre, respectively). Mx-Cre-mediated Gatal recombi-nation, 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, Gatal is necessary for steady-state erythropoiesis and for erythroid expansion in response to anemia. Thus, ablation of Gatal in adult mice results in a condition resembling aplastic crisis in human.
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U2 - 10.1182/blood-2007-09-115121
DO - 10.1182/blood-2007-09-115121
M3 - Article
C2 - 18258797
AN - SCOPUS:43249086780
VL - 111
SP - 4375
EP - 4385
JO - Blood
JF - Blood
SN - 0006-4971
IS - 8
ER -