SLC9A3 and substance dependence: However, it should be recognized that, despite its phenotypic and functional improvements from global Nhe3−/− mice, our results suggest that tgNhe3−/− mice remain to be an inadequate mutant mouse model to determine the relative role or contribution of proximal tubule or kidney NHE3 in the physiological regulation of blood pressure and the development of ANG II-dependent hypertension.