Influence of murine background strain on renal water balance and urine production

The kidneys are essential in maintaining the body’s dynamic water and electrolyte equilibrium. Several mouse strains are widely used in studying renal physiology and diseases with previous observations suggesting background strain influences urine production and diuretic responses in mice. A systematic analysis, however, has not yet been performed and the underlying explanation of these difference remains unclear. The present study aims to examine the differences in water and salt handling between mice of C57Bl/6J and 129S6/SV lineage. Adult male and female mice aged 10-14 weeks were housed in metabolic cages to facilitate urine collection and other measurements, including body weight as well as food and water intake. At the conclusion of the study, mice were sacrificed for blood and tissue collections. We show that while 129SV mice exhibit a decreased 24-hour water intake and urinary output across sex, 129SV females reveal an increase in urine osmolality. Interestingly, urinary excretion of sodium, potassium, and chloride over 24-hours is reduced in 129SV mice. Analysis of blood chemistry reveals male 129SV mice display decreased Na + and increased K + plasma concentrations, with an overall trend of lower plasma osmolalities in both male and female 129SV mice. Western blotting of whole kidney indicates 129SV mice have increased expression of the Na-K-Cl cotransporter (NKCC2) and the sodium-hydrogen exchanger 3 (NHE3), suggesting greater Na + reabsorption in the more proximal portion of the renal tubule. Further analysis by western blot reveals 129SV mice exhibit remarkably more expression of several aquaporins (AQPs). Specifically, 129SV mice have increased expression of AQP1 and AQP3, which is indicative of enhanced water reuptake along the nephron. Taken together, our data suggests the differences in urine production between these two strains can be accounted for by water retention as a consequence of Na + movement within the nephron. Future studies should assess the potential mechanisms responsible for the regulation of and differences in sodium and water handling that contribute to the urinary variations between the C57 and 129SV strains. This study was funded by grants R01 DK130901, R01 DK111380, R01 DK137167, and U54 DK137329 from the National Institutes of Health. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.