The TALE Homeodomain Protein Pbx2 Is Not Essential for Development and Long-Term Survival

Abstract

Pbx2 is one of four mammalian genes that encode closely related TALE homeodomain proteins, which serve as DNA binding partners for a subset of Hox transcription factors. The expression and contributions of Pbx2 to mammalian development remain undefined, in contrast to the essential roles recently established for family members Pbx1 and Pbx3. Here we report that Pbx2 is widely expressed during embryonic development, particularly in neural and epithelial tissues during late gestation. Despite wide Pbx2 expression, mice homozygous mutant for Pbx2 are born at the expected Mendelian frequencies and exhibit no detectable abnormalities in development and organogenesis or reduction of long-term survival. The lack of an apparent phenotype in Pbx2 ؊ / ؊ mice likely reflects functional redundancy, since the Pbx2 protein is present at considerably lower levels than comparable isoforms of Pbx1 and/or Pbx3 in embryonic tissues. In postnatal bone marrow and thymus, however, Pbx2 is the predominant high-molecular-weight (MW)-isoform Pbx protein detectable by immunoblotting. Nevertheless, the absence of Pbx2 has no measurable effect on steady-state hematopoiesis or immune function in adult mice, suggesting possible compensation by low-MW-isoform Pbx proteins present in these tissues. We conclude that the roles of Pbx2 in murine embryonic development, organogenesis, hematopoiesis, immune responses, and long-term survival are not essential.

HOXA/PBX3 knockdown impairs growth and sensitizes cytogenetically normal acute myeloid leukemia cells to chemotherapy

“…23,24 Deletion of TALE genes is also associated with impaired hematopoiesis. Both Meis1 and Pbx1 are essential for definitive hematopoiesis whereas Pbx2 is reported to be dispensable for normal hematopoiesis 25 and Pbx3 deficiency is associated with early death due to central respiratory failure. 26 We provide evidence that defined HOX/TALE gene expression signatures may have specific prognostic value and that targeting clinically relevant HOXA/PBX3 axes may provide therapeutic benefit to patients with CN-AML.…”

The absence ofPrep1causes p53-dependent apoptosis of mouse pluripotent epiblast cells

“…While the single Pbx2 knockout mice are viable and fertile , Pbx3 null mice are born, but die within a few hours owing to central respiratory failure . Importantly, Pbx2 partly compensates for Pbx1 (Capellini et al, 2006;Selleri et al, 2004).…”

Retinoid Signaling is a Context-Dependent Regulator of Embryonic Stem Cells

“…Pbx2* (pre B-cell leukemia transcription factor 2) ((-), see in the text) It has been found that Pbx2 -/-embryos are born at the expected Mendelian frequencies and exhibit no detectable abnormalities in development and organogenesis (Selleri, DiMartino et al 2004), however they show limb abnormalities (Capellini, Di Giacomo et al 2006). Supporting its role in this phenomenon, its elevated expression in limb buds after RA treatment has been demonstrated.…”