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, pre-B-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.
Van Loo
Pieter Fokko
PF
Department of Cell Biology, Erasmus MC, 3000 DR Rotterdam, The Netherlands.
Bouwman
Peter
P
Ling
Kam-Wing
KW
Middendorp
Sabine
S
Suske
Guntram
G
Grosveld
Frank
F
Dzierzak
Elaine
E
Philipsen
Sjaak
S
Hendriks
Rudolf W
RW
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian; D004912:Erythrocytes / Q000166:cytology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics; D022781:Hepatocytes / Q000166:cytology / Q000637:transplantation; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology; D051705:Sp3 Transcription Factor; D013154:Spleen / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; C497122:Sp3 protein, mouse; D014157:Transcription Factors; D051705:Sp3 Transcription Factor