The ETS Transcription Factor GABPα Is Essential for Early Embryogenesis

Abstract

The ETS transcription factor complex GABP consists of the GABPα protein, containing an ETS DNA binding domain, and an unrelated GABPβ protein, containing a transactivation domain and nuclear localization signal. GABP has been shown in vitro to regulate the expression of nuclear genes involved in mitochondrial respiration and neuromuscular signaling. We investigated the in vivo function of GABP by generating a null mutation in the murine Gabpα gene. Embryos homozygous for the null Gabpα allele die prior to implantation, consistent with the broad expression of Gabpα throughout embryogenesis and in embryonic stem cells. Gabpα^+/− mice demonstrated no detectable phenotype and unaltered protein levels in the panel of tissues examined. This indicates that Gabpα protein levels are tightly regulated to protect cells from the effects of loss of Gabp complex function. These results show that Gabpα function is essential and is not compensated for by other ETS transcription factors in the mouse, and they are consistent with a specific requirement for Gabp expression for the maintenance of target genes involved in essential mitochondrial cellular functions during early cleavage events of the embryo.