Gross phenotypes of Pax2/8 double mutant kidneys. (A) Histology of adult kidneys with the indicated genotypes after tamoxifen administration shows no major structural abnormalities of pathology. Slight dilation of IMCDs is seen in the Pax2/8 KOs (right lower panel), which may reflect increased urine output. (B) Water consumption as measured in single-housed metabolic cages of mice with no Pax2/8 deletion (Cre−) or deletions of either Pax2 (P2), Pax8 (P8), or both genes (P28). A significant increase in water consumption was observed in Pax2/8 double KOs (*P<0.001; n=6 per genotype). (C) Urine outputs as collected from metabolic cages over 24-hour periods shows significant increase in urine excretion only in Pax2/8 double KOs (*P<0.001; n=6 per genotype). (D) Osmolality was measured in urines from Pax2/8 double KOs (Cre+) and controls (Cre−). (E) Immunostaining for Pax2 or Pax8 (green) in kidneys from Pax2fl/fl;Pax8fl/fl mice with or without RosaCreEr after tamoxifen administration. (F) Quantitative RT-PCR for Pax2 or Pax8 mRNA from three total kidney RNAs per cohort after tamoxifen treatment of control mice (Cre−), Pax2, Pax8, or Pax2/8 double KOs.