In vivo requirements for transcription factors GATA-1 and GATA-2 during hematopoiesis.

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Firstly, we established GATA-1 conditional knockout mice (G1-CK0) and mated with Mx1-Cre mice to generate G1-CKO::Mx1-Cre. In these mice, the GATA-1 hematopoietic cell specific first exon (IE exon) could be effectively deleted in hematopoietic cells by using injected polyinosinic-polycytidylic acid (pIpC) to induce expression of Cre recombinase. One month after pIpC injection, G1-CKO::Mx1-Cre mice developed severe anemia and thrombocytopenia. Immunophenotypical examination revealed that c-Kit^-CD71^+Ter119^<low> immature erythroid progenitors and GATA-1 deficient megakaryocytes were accumulated in bone marrows and spleens.Secondary, We established and GATA-2 conditional knockout mice (G2-CKO) in which GATA-2 cDNA sandwiched between two loxP sequences was inserted into the translation initiation site of Oata2 gene. To investigate the function of GATA-2 on the hematopoietic cell proliferation in vivo, we established compound mice with Mx1-Cre (G2-CK0::Mx1-Cre) The number of Lin^-c-Kit^+Sca1^+ hematopoietic stem cells for the G2-CKO::Mx1-Cre mice significantly declined compared with those for the control mice after pIpC injection. These findings indicate that the maintenance of hematopoietic stem cells by GATA-2 and the regulation of erythroid/megakaryocytic cell development by GATA-1 are important for adult hematopoiesis.