title: Bladder outlet obstruction in male cystinuria mice.
abstract: BACKGROUND
  Cystinuria is the most common inherited cause of urinary tract stones in children. It can lead to obstructive uropathy, which is a major cause of renal failure. Genetic studies have identified two genes, SLC3A1 and SLC7A9, to be directly involved in cystine stone formation. Slc3a1 knockout male mice develop cystine stones in the bladder and, to a lesser extent, in the kidney. Slc3a1 knockout female mice also develop cystinuria, but they do not form stones. The specific aim of this study was to characterize bladder function in cystinuria mice.
  
  
  METHODS
  Eight control (4 male, 4 female) and 16 Slc3a1 knockout (9 male, 7 female) mice of mixed strain background (C57B/129, age 4-5 months) were evaluated. Each mouse was anesthetized and the bladder dome catheterized for cystometry. Immediately following cystometry, the bladder was excised, weighed, and separated into three full thickness strips for contractile studies.
  
  
  RESULTS
  Bladders from cystinuria male mice had significantly increased weight, all of them had stones, decreased compliance, and decreased contractile responses to field stimulation, ATP, carbachol, and KCl. Compared with controls, female knockout mice showed normal bladder weight, decreased voiding pressure, slightly decreased compliance, and slightly decreased contractile responses.
  
  
  CONCLUSIONS
  These studies clearly demonstrate that the bladder stones that developed in the male cystinuria mice resulted in a partial outlet obstruction. Although the female cystinuria mice did not have bladder stones, bladder function was mildly impaired; presumably by the presence of cystine crystals.
authors.affiliation: Department of Surgery, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ, USA.
authors.forename: Mathew
authors.initials: M
authors.lastname: Ercolani
authors.forename: Amrik
authors.initials: A
authors.lastname: Sahota
authors.forename: Catherine
authors.initials: C
authors.lastname: Schuler
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Evan
authors.forename: David
authors.initials: D
authors.lastname: Reimer
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Barone
authors.forename: Jay A
authors.initials: JA
authors.lastname: Tischfield
authors.forename: Robert M
authors.initials: RM
authors.lastname: Levin
mesh_terms: D000818:Animals; D003555:Cystinuria / Q000150:complications*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D001744:Urinary Bladder Calculi / Q000150:complications*; D001748:Urinary Bladder Neck Obstruction / Q000209:etiology*