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Updated: May 9, 2026
A Mouse Model to Evaluate the Long-Term Structural and Functional Outcomes after the Reversal of Prolonged Unilateral Ureteric Obstruction
Published on: July 18, 2025
Urinary tract obstruction in the mouse: the kinetics of distal nephron injury
Michael J Hiatt1, Larissa Ivanova, Peter Trnka
1Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
Insights
Congenital urinary tract obstruction in children causes chronic kidney disease. Postnatal mouse models effectively replicate fetal collecting duct injury, revealing significant distal nephron damage and adhesion disruption.
Area of Science:
- Nephrology
- Pediatric Nephrology
- Developmental Biology
Background:
- Congenital urinary tract obstruction is a primary cause of childhood chronic kidney disease.
- Fetal obstruction impairs kidney development, differentiation, and maturation.
- Postnatal rodent models often overlook collecting duct and distal nephron pathology.
Purpose of the Study:
- To investigate distal nephron injury in a postnatal mouse model of unilateral ureteric obstruction (UUO).
- To assess the suitability of the postnatal mouse UUO model for studying collecting duct and distal tubule pathology.
- To identify mechanisms of distal nephron injury and its contribution to kidney fibrosis.
Main Methods:
- Utilized the mouse unilateral ureteric obstruction (UUO) model.
- Examined time points from 1 to 14 days of obstruction.
- Assessed myofibroblast accumulation, tubule dilatation, aquaporin 2 expression, intercalated cell abundance, and epithelial adhesion.
Main Results:
- The postnatal mouse UUO model replicated key features of fetal collecting duct injury.
- Obstruction led to a sixfold increase in myofibroblast accumulation.
- Significant dilatation of distal nephron tubules, reduced aquaporin 2 expression, decreased intercalated cell abundance, and disrupted epithelial adhesion were observed.
- These pathologies affected distal and connecting tubules.
Conclusions:
- Distal nephron pathology is a significant component of postnatal mouse UUO.
- The postnatal mouse UUO model is a valuable tool for studying collecting duct and distal tubule injury.
- This model can elucidate mechanisms underlying distal nephron contributions to kidney repair and fibrosis.
Abstract:
Congenital urinary tract obstruction is the single most important cause of childhood chronic kidney disease. We have previously demonstrated that human and primate fetal obstruction impairs the development, differentiation, and maturation of the kidney. Research using postnatal rodent models has primarily focused upon the role of proximal tubular injury, with few reports of collecting duct system pathology or the suitability of the postnatal models for examining injury to the distal nephron. We have employed the mouse unilateral ureteric obstruction (UUO) model and examined time points ranging from 1 to 14 days of obstruction. Many of the key features of fetal collecting duct injury are replicated in the postnatal mouse model of obstruction. Obstruction causes a sixfold increase in myofibroblast accumulation, two- to threefold dilatation of tubules of the distal nephron, 65% reduction of principal cell aquaporin 2 expression, 75% reduction of collecting duct intercalated cell abundance, and disruption of E-cadherin- and βcatenin-mediated collecting duct epithelial adhesion. Notably, these features are shared by the distal and connecting tubules. This work confirms that distal nephron pathology is a significant component of postnatal mouse UUO. We have highlighted the utility of this model for investigating collecting duct and distal tubule injury and for identifying the underlying mechanisms of the distal nephron's contribution to the repair and fibrosis.
