title: Development of an animal model to study congenital urinary obstruction.
abstract: OBJECTIVE
  We outline the development of a reliable model of obstructive uropathy in fetal lambs highlighting our understanding of the critical time points for interventions and the variability of any such model. We identify some discoveries that may have clinical implications.
  
  
  METHODS
  The model requires 60-day-gestation fetal lambs. In lambs, glomerulogenesis is complete by 90 days gestation. (Term is 145 days.) The ability to develop a reliable method of creating bladder outlet obstruction in females, ligating both the urethra and urachus was critical. The lambs are bred to an accuracy of ±24 h.
  
  
  RESULTS
  Creating the model at 50-60 days gestation, produces different expressions of renal dysplasia in groups of lambs undergoing identical interventions at the same stage of gestation. Early complete urethral obstruction can produce the Potter phenotype. An appropriately timed vesico-amniotic shunt preserves renal development, producing a shrunken, non-compliant bladder. Shunting the normal fetal bladder at 80 days gestation produces a similar bladder. Provision of a low-pressure valve in the shunt preserves bladder development and compliance. Using a high-pressure shunt produces results similar to non-shunted lambs.
  
  
  CONCLUSIONS
  We developed a reliable animal model for obstructive uropathy. Being alert to peripheral results can lead to new findings.
authors.affiliation: Department of Obstetrics and Gynaecology, School of Medicine and Health Sciences, University of Otago, Wellington, P.O. Box 7343, Wellington South, 6242, Wellington, New Zealand, kevin.pringle@otago.ac.nz.
authors.forename: K C
authors.initials: KC
authors.lastname: Pringle
authors.forename: H
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Seki
authors.forename: J
authors.initials: J
authors.lastname: Koike
authors.forename: J
authors.initials: J
authors.lastname: Zuccollo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000601:surgery*; D011247:Pregnancy; D011270:Pregnancy, Animal; D012756:Sheep; D014524:Urethral Obstruction / Q000151:congenital / Q000196:embryology / Q000601:surgery*; D001743:Urinary Bladder / Q000196:embryology / Q000601:surgery; D001748:Urinary Bladder Neck Obstruction / Q000151:congenital / Q000196:embryology / Q000601:surgery*; D013520:Urologic Surgical Procedures / Q000379:methods*