GSE84780 Hyperactivation of Nrf2 in early tubular development induces nephrogenic diabetes insipidus

Contributors : Takafumi Suzuki ; Shiori Seki ; Keiichiro Hiramoto ; Eriko Naganuma ; Eri H Kobayashi ; Ayaka Yamaoka ; Liam Baird ; Nobuyuki Takahashi ; Hiroshi Sato ; Masayuki YamamotoSeries Type : Expression profiling by arrayOrganism : Mus musculusNF-E2-related factor-2 (Nrf2) regulates the cellular response to oxidative/electrophilic stresses, and loss of Keap1 increases the Nrf2 protein level. As Keap1-null mice die of esophageal hyperkeratosis, whole-body phenotypes of Nrf2 hyperactivation in adult animals remain to be delineated. Here we show that deleting esophageal Nrf2 in Keap1-null mice the mice survive until adulthood, but develop polyuria with low osmolality and bilateral hydronephrosis. This novel phenotype is to be attributable to defects in water reabsorption caused by a reduction in the level of the aquaporin 2 (AQP2) channel in the kidney. In line, renal tubular deletion of Keap1 generates symptoms of nephrogenic diabetes insipidus, demonstrating that Nrf2 activation in developing tubular cells causes a water reabsorption defect. The rescue of mice from the lethal first hit of Keap1 ablation serves as a useful tool to study novel functions of Nrf2.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Mus musculus Source Type: research