Role of GATA-1 in proliferation and differentiation of definitive erythroid and megakaryocytic cells in vivo. Blood

To elucidate the contributions of GATA-1 to definitive hema-topoiesis in vivo, we have examined adult mice that were rendered genetically defective in GATA-1 synthesis (Takaha-shi et al, J Biol Chem 272:12611, 1997). Because the GATA-1 gene is located on the X chromosome, which is randomly inactivated in every cell, heterozygous females can bear either an active wild-type or mutant (referred to as GATA-1.05) GATA-1 allele, consequently leading to variable anemic severity. These heterozygous mutant mice usually devel-oped normally, but they began to die after 5 months. These affected animals displayed marked splenomegaly, anemia, and thrombocytopenia. Proerythroblasts and megakaryo-cytes massively accumulated in the spleens of the heterozy-gotes, and we showed that the neomycin resistance gene (which is the positive selection marker in ES cells) wa