title: Urinary tract obstruction in the mouse: the kinetics of distal nephron injury.
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.
authors.affiliation: Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hiatt
authors.forename: Larissa
authors.initials: L
authors.lastname: Ivanova
authors.forename: Peter
authors.initials: P
authors.lastname: Trnka
authors.forename: Marc
authors.initials: M
authors.lastname: Solomon
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Matsell
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015820:Cadherins / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D007685:Kidney Tubules, Collecting / Q000737:chemistry / Q000166:cytology / Q000473:pathology; D007700:Kinetics; D008297:Male; D051379:Mice; D009399:Nephrons / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D018709:Statistics, Nonparametric; D014517:Ureteral Obstruction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D024141:Collagen Type IV; D051176:beta Catenin