Alterations in bladder function associated with urothelial defects in uroplakin II and IIIa knockout mice

Tamer Aboushwareb, Ge Zhou, Fang Ming Deng, Chanda Turner, Karl Erik Andersson, Moses Tar, Weixin Zhao, Arnold Melman, Ralph D'Agostino, Tung Tien Sun, George J. Christ

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Aims: 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.

Original languageEnglish (US)
Pages (from-to)1028-1033
Number of pages6
JournalNeurourology and Urodynamics
Volume28
Issue number8
DOIs
StatePublished - Nov 1 2009

Keywords

  • BOO
  • LUTS
  • Urodynamics

ASJC Scopus subject areas

  • Clinical Neurology
  • Urology

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    Aboushwareb, T., Zhou, G., Deng, F. M., Turner, C., Andersson, K. E., Tar, M., Zhao, W., Melman, A., D'Agostino, R., Sun, T. T., & Christ, G. J. (2009). Alterations in bladder function associated with urothelial defects in uroplakin II and IIIa knockout mice. Neurourology and Urodynamics, 28(8), 1028-1033. https://doi.org/10.1002/nau.20688