title: Alterations in bladder function associated with urothelial defects in uroplakin II and IIIa knockout mice.
abstract: OBJECTIVE
  The effects of deleting genes encoding uroplakins II (UPII) and III (UPIIIa) on mouse bladder physiology/dysfunction were studied in male and female wild type and knockout (KO) mice.
  
  
  METHODS
  UPII, UPIIIa, and WT mice were catheterized using previously described techniques. Continuous cystometry was conducted in conscious, freely moving animals. Bladder strips were harvested after animal sacrifice and pharmacological studies and EFS were conducted in an organ chamber. Histological studies were also carried on with H&E staining to identify differences among the three mouse types.
  
  
  RESULTS
  These studies have revealed numerous alterations, some of which were apparently gender-specific. Nonvoiding contractions were common in both UPII and UPIIIa KO mice, although more severe in the former. In particular, the increased bladder capacity, micturition pressure and demonstrable nonvoiding contractions observed in the male UPII KO's, were reminiscent of an obstruction-like syndrome accompanied by evidence of emerging bladder decompensation, as reflected by an increased residual volume. Pharmacological studies revealed a modest, gender-specific reduction in sensitivity of isolated detrusor strips from UPII KO female mice to carbachol-induced contractions. A similar reduction was observed in UPIIIa KO female mice. Histological investigation showed urothelial hyperplasia in both UPII KO and UPIIIa KO mice, although again, apparently more severe in the former.
  
  
  CONCLUSIONS
  These results confirm and extend previous work to indicate that urothelial defects due to uroplakin deficiency are associated with significant alterations in bladder function and further highlight the importance of the urothelium to bladder physiology/dysfunction.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Tamer
authors.initials: T
authors.lastname: Aboushwareb
authors.forename: Ge
authors.initials: G
authors.lastname: Zhou
authors.forename: Fang-Ming
authors.initials: FM
authors.lastname: Deng
authors.forename: Chanda
authors.initials: C
authors.lastname: Turner
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.forename: Moses
authors.initials: M
authors.lastname: Tar
authors.forename: Weixin
authors.initials: W
authors.lastname: Zhao
authors.forename: Arnold
authors.initials: A
authors.lastname: Melman
authors.forename: Ralph
authors.initials: R
authors.lastname: D'Agostino
authors.forename: Tung-Tien
authors.initials: TT
authors.lastname: Sun
authors.forename: George J
authors.initials: GJ
authors.lastname: Christ
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D001743:Urinary Bladder / Q000503:physiopathology*; D060170:Uroplakin II; D060171:Uroplakin III
chemical_list: D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C554659:Upk2 protein, mouse; D060170:Uroplakin II; D060171:Uroplakin III