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.

We thank Joseph Lipsick and Uta Francke for many helpful discussions; Michael Depew, Inma Cobos, and Stewart Anderson for comments on the manuscript; and Cita Nicolas, Maria Ambrus, and Lawryn Kasper for expert technical assistance.

These studies were supported by grants to M.L.C. from the National Institutes of Health (CA42971, CA70704, and CA90735) and to L.S. from the March of Dimes and Birth Defects Foundation (6-FY03-071) and the National Institutes of Health (HD043997-01 A1).