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Prepublished online as a Blood First Edition Paper on April 3, 2003; DOI 10.1182/blood-2002-06-1848.

Submitted June 21, 2002
Accepted February 25, 2003
Impaired hematopoiesis in mice lacking the transcription factor Sp3
Pieter F van Loo, Peter Bouwman, Kam-Wing Ling, Sabine Middendorp, Guntram Suske, Frank Grosveld, Elaine Dzierzak, Sjaak Philipsen*, and Rudolf W Hendriks
Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands
Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
Institut fuer Molekularbiologie und Tumorforschung, Philipps-Universitaet Marburg, Marburg, Germany
* Corresponding author; email: philipsen{at}ch1.fgg.eur.nl.
As the zinc-finger transcription factor Sp3 has been implicated in the regulation of many hematopietic-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, pre-B cell proliferation and differentiation into 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.

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