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

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.