Impaired hematopoiesis in mice lacking the transcription factor Sp3

As the zinc-finger transcription factor specificity protein 3 (Sp3) has been implicated in the regulation of many hematopoietic-specific genes, we analyzed the role of Sp3 in hematopoiesis. At embryonic day 18.5 (E18.5), Sp3(-/-) mice exhibit a partial arrest of T-cell development in the thymus and B-cell numbers are reduced in liver and spleen. However, preB-cell proliferation and differentiation into immunoglobulin M-positive (IgM(+)) B cells in vitro are not affected. At E14.5 and E16.5, Sp3(-/-) mice exhibit a significant delay in the appearance of definitive erythrocytes in the blood, paralleled by a defect in the progression of differentiation of definitive erythroid cells in vitro. Perinatal death of the null mutants precludes the analysis of adult hematopoiesis in Sp3(-/-) mice. We therefore investigated the ability of E12.5 Sp3(-/-) liver cells to contribute to the hematopoietic compartment in an in vivo transplantation assay. Sp3(-/-) cells were able to repopulate the B- and T-lymphoid compartment, albeit with reduced efficiency. In contrast, Sp3(-/-) cells showed no significant engraftment in the erythroid and myeloid lineages. Thus, the absence of Sp3 results in cell-autonomous hematopoietic defects, affecting in particular the erythroid and. myeloid cell lineages.