Involvement of Prep1 in the alpha beta T-Cell Receptor T-Lymphocytic Potential of Hematopoietic Precursors

Prep1 is a homeodomain transcription factor that acts by dimerizing with Pbx. Since Prep1 null embryos die at gastrulation, we studied Prep1 super(i/i) hypomorphic mice to study the physiological role of Prep1. A low percentage of homozygous Prep1 super(i/i) mice survived at birth, and their postnat...

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Published in:Molecular and cellular biology 2005-12, Vol.25 (24), p.10768-10781
Main Authors: Penkov, Dmitri, Di Rosa, Patrizia, Fernandez Diaz, Luis, Basso, Veronica, Ferretti, Elisabetta, Grassi, Fabio, Mondino, Anna, Blasi, Francesco
Format: Article
Language:English
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Summary:Prep1 is a homeodomain transcription factor that acts by dimerizing with Pbx. Since Prep1 null embryos die at gastrulation, we studied Prep1 super(i/i) hypomorphic mice to study the physiological role of Prep1. A low percentage of homozygous Prep1 super(i/i) mice survived at birth, and their postnatal functions could be investigated. Reduced Prep1 expression caused an abnormal thymic T-cell development: increased CD4 super(-) CD8 super(-) double-negative thymocytes, decrease in alpha beta TCR super(high) cells (cells with high levels of the alpha beta T-cell receptor [ alpha beta TCR]) and CD4 super(+) and CD8 super(+) single-positive (SP) thymocytes, and increase in gamma delta TCR cells. Peripheral lymphoid organs of Prep1 super(i/i) mice contained fewer alpha beta TCR mature T cells and more gamma delta TCR T cells than wild-type littermates. Moreover, Prep1 super(i/i) CD4 super(+) CD8 super(+) double-positive thymocytes underwent more apoptosis, and SP thymocytes proliferated less than control littermates. Mice that were lethally irradiated and then had Prep1 super(i/i) fetal liver cells transplanted showed the same defects as the Prep1 super(i/i) mice did. Among PBC family members, Pbx2 and very low levels of Pbx3 were observed in the thymi of wild-type mice. In Prep1 super(i/i) mice, the level of Pbx2 protein was profoundly decreased, while for Pbx3 no definitive conclusion could be reached. Therefore, the deficient postnatal T-lymphocytic potential of the Prep1 hematopoietic progenitors depends on the combined, not compensated, absence of Prep1 and at least Pbx2.
ISSN:0270-7306
1098-5549
DOI:10.1128/MCB.25.24.10768-10781.2005