Further analysis of the orpk mouse model of human autosomal recessive polycystic kidney disease is providing more insight into the function of the Tg737 gene and the pathobiology of renal cystic disease. Here we have determined the temporal-spatial profile of Tg737 expression and ascertained the profile of disease pathology utilizing Tg737delta2-3betaGal/+ and Tg737delta2-3betaGal/ Tg737orpk compound heterozygotes from embryonic day 13.0 (E13.0) to postnatal day 270 (D270). This has allowed us to correlate disease progression and Tg737 expression in the context of the mutant orpk phenotype. These data reveal that Tg737 is dynamically regulated during kidney development and during postnatal kidney maturation in normal and in orpk mutants. This expression pattern correlates with the pathology of the disease, such that tubular segments with the highest expression levels are most protected from cystic disease. These data indicate that kidney tubules require a threshold level of Tg737 function for normal tubular development, structure, and function. In addition, these data demonstrate that the timing of cyst formation and severity of cyst progression is modulated differently in different regions of the nephron in this model.