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

GATA-1 is a transcription factor essential for erythroid/megakaryocytic cel l differentiation. To investigate the contribution of individual domains of GATA-1 to its activity, transgenic mice expressing either an N-terminus, o r an N- or C-terminal zinc finger deletion of GATA-1 (Delta NT, Delta NF or Delta CF, respectively) were generated and crossed to GATA-1 germline muta nt (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 Delta NF and Delta CF t ransgenes failed to rescue the GATA-1.051Y pups. However, transgenic mice e xpressing Delta NT, but not the Delta NF protein, were able to rescue defin itive hematopoiesis. In embryos, while neither the Delta CF protein nor a m utant missing both N-terminal domains (Delta NTNF) was able to support prim itive erythropoiesis, the two independent Delta NT and Delta NF mutants cou ld support primitive erythropoiesis. Thus, lineage-specific transgenic resc ue of the GATA-1 mutant mouse revealed novel properties that are conferred by specific domains of GATA-1 during primitive and definitive erythropoiesi s, and demonstrate that the NT and NF moieties lend complementary, but dist inguishable properties to the function of GATA-1.