Urogenital alterations in aged male Caveolin-1 knockout mice

Scott E. Woodman, Michelle W C Cheung, Moses Tarr, Amanda C. North, William Schubert, Guy Lagaud, Carolyn B. Marks, Robert G. Russell, Ghada S. Hassan, Stephen M. Factor, George J. Christ, Michael P. Lisanti

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Purpose: Caveolae are flask-shaped invaginations of the plasma membrane formed by the oligomerization of caveolins Because only smooth muscle contains all caveolin (Cav) family members (Cav-1, 2 and 3), we examined the contribution of each caveolin to urogenital smooth muscle structure/function. Materials and Methods: WT, Cav-1, 2, 3 and -1/3 knockout (KO) mouse bladders were characterized by Western blot, co-immunoprecipitation, immunofluoreseence microscopy, electron microscopy, histochemistry and pharmacological techniques. Cystometric analysis was performed in conscious, freely moving mice. Other urogenital organs were investigated by histological analysis. Results: The loss of bladder Cav-1 results in a marked decrease in Cav-2 but not Cav-3 expression. Ablation of Cav-3 fails to alter Cav-1 or Cav-2 expression. Deletion of Cav-1 results in the almost complete loss of caveolae, while Cav-2 KO and Cav-3 KO mouse smooth muscle showed a normal number of caveolae. The loss of Cav-1 generated caveolae led to significant urogenital changes in male mice (most marked by 12 months of age), namely 1) bladder weight-to-body weight ratios were increased, 2) the bladder smooth muscle layer was thickened, 3) the bladders had increased baseline, threshold and spontaneous pressures, 4) bladder strips showed a decreased contractile response to carbachol and KCl, and 5) these smooth muscle changes were accompanied by marked fluid accumulation in the prostate and seminal vesicles, with intracellular vacuolization in the kidneys. As such, male Cav-1 KO mice may be a useful animal model for studying LUTD (lower urinary tract dysfunction) that is so prevalent in aging male patients. Conclusions: The loss of Cav-1 and, thus, of most smooth muscle cell caveolae results in significant bladder dysfunction and urogenital organ changes in aged male mice.

Original languageEnglish (US)
Pages (from-to)950-957
Number of pages8
JournalJournal of Urology
Volume171
Issue number2 I
DOIs
StatePublished - Feb 2004

Fingerprint

Caveolin 1
Caveolin 2
Knockout Mice
Caveolae
Caveolin 3
Urinary Bladder
Smooth Muscle
Caveolins
Seminal Vesicles
Carbachol
Urinary Tract
Immunoprecipitation
Smooth Muscle Myocytes
Prostate
Microscopy
Electron Microscopy
Animal Models
Western Blotting
Body Weight
Cell Membrane

Keywords

  • Bladder, muscle, smooth
  • Caveolae
  • Caveolins
  • Seminal vesicles

ASJC Scopus subject areas

  • Urology

Cite this

Woodman, S. E., Cheung, M. W. C., Tarr, M., North, A. C., Schubert, W., Lagaud, G., ... Lisanti, M. P. (2004). Urogenital alterations in aged male Caveolin-1 knockout mice. Journal of Urology, 171(2 I), 950-957. https://doi.org/10.1097/01.ju.0000105102.72295.b8

Urogenital alterations in aged male Caveolin-1 knockout mice. / Woodman, Scott E.; Cheung, Michelle W C; Tarr, Moses; North, Amanda C.; Schubert, William; Lagaud, Guy; Marks, Carolyn B.; Russell, Robert G.; Hassan, Ghada S.; Factor, Stephen M.; Christ, George J.; Lisanti, Michael P.

In: Journal of Urology, Vol. 171, No. 2 I, 02.2004, p. 950-957.

Research output: Contribution to journalArticle

Woodman, SE, Cheung, MWC, Tarr, M, North, AC, Schubert, W, Lagaud, G, Marks, CB, Russell, RG, Hassan, GS, Factor, SM, Christ, GJ & Lisanti, MP 2004, 'Urogenital alterations in aged male Caveolin-1 knockout mice', Journal of Urology, vol. 171, no. 2 I, pp. 950-957. https://doi.org/10.1097/01.ju.0000105102.72295.b8
Woodman, Scott E. ; Cheung, Michelle W C ; Tarr, Moses ; North, Amanda C. ; Schubert, William ; Lagaud, Guy ; Marks, Carolyn B. ; Russell, Robert G. ; Hassan, Ghada S. ; Factor, Stephen M. ; Christ, George J. ; Lisanti, Michael P. / Urogenital alterations in aged male Caveolin-1 knockout mice. In: Journal of Urology. 2004 ; Vol. 171, No. 2 I. pp. 950-957.
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abstract = "Purpose: Caveolae are flask-shaped invaginations of the plasma membrane formed by the oligomerization of caveolins Because only smooth muscle contains all caveolin (Cav) family members (Cav-1, 2 and 3), we examined the contribution of each caveolin to urogenital smooth muscle structure/function. Materials and Methods: WT, Cav-1, 2, 3 and -1/3 knockout (KO) mouse bladders were characterized by Western blot, co-immunoprecipitation, immunofluoreseence microscopy, electron microscopy, histochemistry and pharmacological techniques. Cystometric analysis was performed in conscious, freely moving mice. Other urogenital organs were investigated by histological analysis. Results: The loss of bladder Cav-1 results in a marked decrease in Cav-2 but not Cav-3 expression. Ablation of Cav-3 fails to alter Cav-1 or Cav-2 expression. Deletion of Cav-1 results in the almost complete loss of caveolae, while Cav-2 KO and Cav-3 KO mouse smooth muscle showed a normal number of caveolae. The loss of Cav-1 generated caveolae led to significant urogenital changes in male mice (most marked by 12 months of age), namely 1) bladder weight-to-body weight ratios were increased, 2) the bladder smooth muscle layer was thickened, 3) the bladders had increased baseline, threshold and spontaneous pressures, 4) bladder strips showed a decreased contractile response to carbachol and KCl, and 5) these smooth muscle changes were accompanied by marked fluid accumulation in the prostate and seminal vesicles, with intracellular vacuolization in the kidneys. As such, male Cav-1 KO mice may be a useful animal model for studying LUTD (lower urinary tract dysfunction) that is so prevalent in aging male patients. Conclusions: The loss of Cav-1 and, thus, of most smooth muscle cell caveolae results in significant bladder dysfunction and urogenital organ changes in aged male mice.",
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AU - Lagaud, Guy

AU - Marks, Carolyn B.

AU - Russell, Robert G.

AU - Hassan, Ghada S.

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