Transgenic over-expression of GATA-1 mutant lacking N-finger domain causes hemolytic syndrome in mouse erythroid cells

Mayu Nakano, Kinuko Ohneda, Harumi Yamamoto-Mukai, Ritsuko Shimizu, Osamu Ohneda, Sakie Ohmura, Mikiko Suzuki, Saho Tsukamoto, Toru Yanagawa, Hiroshi Yoshida, Yuichi Takakura, Masayuki Yamamoto

研究成果: Article査読

11 被引用数 (Scopus)

抄録

Transcription factor GATA-1 is essential for erythroid cell differentiation. GATA-binding motifs have been found in the regulatory regions of various erythroid-specific genes, suggesting that GATA-1 contributes to gene regulation during the entire process of erythropoiesis. A GATA-1 germ-line mutation results in embryonic lethality due to defective primitive erythropoiesis and GATA-1-null embryonic stem cells fails to differentiate beyond the proerythroblast stage. Therefore, the precise roles of GATA-1 in the later stages of erythropoiesis could not be clarified. Under the control of a GATA-1 gene hematopoietic regulatory domain, a GATA-1 mutant lacking the N-finger domain (ΔNF mutant) was over-expressed in mice. These mice exhibited abnormal morphology in peripheral red blood cells (RBCs), reticulocytosis, splenornegaly, and erythroid hyperplasia, indicating compensated hemolysis. These mice were extremely sensitive to phenylhydrazine (PHZ), an agent that induces hemolysis, and their RBCs were osmotically fragile. Importantly, the hemolytic response to PHZ was partially restored by the simultaneous expression of wild-type GATA-1 with the ΔNF mutant, supporting our contention that ΔNF protein competitively inhibits the function of endogenous GATA-1. These data provide the first in vivo evidence that the NF domain contributes to the gene regulation that is critical for differentiation and survival of mature RBCs in postnatal erythropoiesis.

本文言語English
ページ(範囲)47-62
ページ数16
ジャーナルGenes to Cells
10
1
DOI
出版ステータスPublished - 2005 1
外部発表はい

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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