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 language | English |
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Pages (from-to) | 5250-5260 |
Number of pages | 11 |
Journal | EMBO Journal |
Volume | 20 |
Issue number | 18 |
DOIs | |
Publication status | Published - 2001 Sep 17 |
Externally published | Yes |
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)