Renal concentrating ability in mice: A model for the use of genetic variation in elucidating relationships between structure and function

Summary In Os/+ mice of the XVIII strain, nephron number was reduced by 80% and GFR by 50%. Plots of (U/P)_Osm against percentage filtered solute load excreted showed that the consequent osmotic diuresis per nephron was a sufficient explanation for the mild concentrating defect in XVIII Os/+ mice. This conclusion was confirmed by the fact that subtotal nephrectomy mimicked the effect of the Os gene in this strain. However the same experiments demonstrated that there was an additional qualitative impairment of the renal concentrating mechanism in mice of the DI strain having oligosyndactyly (DI Os/+). Observations on a genetically segregating backcross generation showed that a reduction in mean length of short loops of Henle, but not the absence of a pars recta of the proximal tubule, was probably responsible for the severe concentrating defect in DI Os/+ mice. The usefulness and specific limitations of genetic variation in physiological investigations are discussed.