Transcriptional regulation of Na+/H+ exchanger expression in the intact mouse.

We examined regulation of the Na+/H+ exchanger (NHE1 isoform) in the developing mouse. We generated transgenic mice with the Na+/H+ exchanger promoter directing expression of the beta-Galactosidase reporter. We found that expression of the Na+/H+ exchanger was maximum in the heart and liver of 12-day-old embryonic mice. Similar results were found in mice using the green fluorescent protein reporter driven by the Na+/H+ exchanger promoter. Detailed examination of the myocardium revealed that the GFP reporter protein was expressed in the cytoplasm of cardiomyocyte cells. We examined NHE1 protein expression in transgenic mice lacking the transcription factors AP-2alpha or the transcription factor COUP-TF1. Eighteen-day-old AP-2alpha heterozygote mice show no large changes in NHE1 expression in heart, lung, liver, kidney and brain. In contrast, 18-day-old embryos from AP-2alpha null mice showed a large increase in Na+/H+ exchanger protein expression in the brain. NHE1 protein levels in COUP-TF1 knockout embryos did not differ from wild type embryos. The results suggest that AP-2alpha and COUP-TF1 are not critical to NHE1 expression in the late stage embryo and that other related transcription factors may function in regulation of the Na+/H+ exchanger.