Ablation of Gatal in adult mice results in aplastic crisis, revealing its essential role in steady-state and stress erythropoiesis

Laura Gutiérrez, Saho Tsukamoto, Mikiko Suzuki, Harumi Yamamoto-Mukai, Masayuki Yamamoto, Sjaak Philipsen, Kinuko Ohneda

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4375-4385
Number of pages11
JournalBlood
Volume111
Issue number8
DOIs
Publication statusPublished - 2008 Apr 15

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Ablation of Gatal in adult mice results in aplastic crisis, revealing its essential role in steady-state and stress erythropoiesis'. Together they form a unique fingerprint.

  • Cite this