In vivo requirements for GATA-1 functional domains during primitive and definitive erythropoiesis

Ritsuko Shimizu, Satoru Takahashi, Kinuko Ohneda, James Douglas Engel, Masayuki Yamamoto

Research output: Contribution to journalArticlepeer-review

107 Citations (Scopus)

Abstract

GATA-1 is a transcription factor essential for erythroid/megakaryocytic cell differentiation. To investigate the contribution of individual domains of GATA-1 to its activity, transgenic mice expressing either an N-terminus, or an N- or C-terminal zinc finger deletion of GATA-1 (ΔNT, ΔNF or ΔCF, respectively) were generated and crossed to GATA-1 germline mutant (GATA-1.05) mice. Since the GATA-1 gene is located on the X-chromosome, male GATA-1 mutants die by embryonic day 12.5. Both ΔNF and ΔCF transgenes failed to rescue the GATA-1.05/Y pups. However, transgenic mice expressing ΔNT, but not the ΔNF protein, were able to rescue definitive hematopoiesis. In embryos, while neither the ΔCF protein nor a mutant missing both N-terminal domains (ΔNTNF) was able to support primitive erythropoiesis, the two independent ΔNT and ΔNF mutants could support primitive erythropoiesis. Thus, lineage-specific transgenic rescue of the GATA-1 mutant mouse revealed novel properties that are conferred by specific domains of GATA-1 during primitive and definitive erythropoiesis, and demonstrate that the NT and NF moieties lend complementary, but distinguishable properties to the function of GATA-1.

Original languageEnglish
Pages (from-to)5250-5260
Number of pages11
JournalEMBO Journal
Volume20
Issue number18
DOIs
Publication statusPublished - 2001 Sep 17

Keywords

  • Domain
  • Erythropoiesis
  • GATA-1
  • Rescue
  • Transgenic mouse

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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