MP21-18 CONDITIONAL DELETION OF MANGANESE SUPEROXIDE DISMUTASE IN DETRUSOR SMOOTH MUSCLE IS ASSOCIATED WITH BLADDER OVERACTIVITY IN MICE

Abstract

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology II1 Apr 2015MP21-18 CONDITIONAL DELETION OF MANGANESE SUPEROXIDE DISMUTASE IN DETRUSOR SMOOTH MUSCLE IS ASSOCIATED WITH BLADDER OVERACTIVITY IN MICE Rania Elrashidy, Guiming Liu, Nan Xiao, Michael Kavran, Yexiang Huang, Mingfang Tao, Hoda Mohammad, C Thomas Powell, and Firouz Daneshgari Rania ElrashidyRania Elrashidy More articles by this author , Guiming LiuGuiming Liu More articles by this author , Nan XiaoNan Xiao More articles by this author , Michael KavranMichael Kavran More articles by this author , Yexiang HuangYexiang Huang More articles by this author , Mingfang TaoMingfang Tao More articles by this author , Hoda MohammadHoda Mohammad More articles by this author , C Thomas PowellC Thomas Powell More articles by this author , and Firouz DaneshgariFirouz Daneshgari More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.970AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Manganese superoxide dismutase (MnSOD) represents the first line of defense against oxidative stress (OS). Emerging evidence suggests a key role for OS in the pathogenesis of bladder dysfunction in several disorders. We aimed to generate a mouse model with conditional, smooth muscle (SM)-specific deletion of the Sod2 that encodes MnSOD, to explore the pathological consequences of OS on function of the SM-rich bladder. METHODS Conditional SM-specific Sod2 knockout (KO) mice were generated by crossing mice having floxed Sod2 alleles with mice containing heterozygous knock-in of a gene encoding a tamoxifen-activated Cre in the SM22α promoter locus (SM-CreERT2(ki)Cre/+), in which Cre expression is restricted to SM. Eight-week old male Sod2 lox/lox, SM-CreERT2(ki)Cre/+ mice were injected with 40 mg/kg of 4-hydroxytamoxifen (OHT) for 5 consecutive days to induce Cre-mediated excision of floxed Sod2 alleles. SM-specific Sod2 KO mice were compared with age-matched OHT-treated wild type and SM-specific Cre mice, as controls, at twelve weeks after OHT injection. Conditional deletion of Sod2 and depletion of MnSOD in SM were confirmed by PCR, Western blot, and immunohistochemistry. Nitrotyrosine was measured as a common OS marker. Bladder function was evaluated by measurement of 24-hour micturition habits and conscious cystometry. Bladder morphology was determined by Masson's Trichrome staining. RESULTS MnSOD immunoreactivity was exclusively lost in detrusor SM and other SM-containing tissues in SM-specific Sod2 KO mice, associated with a dramatic decline in the enzymatic activity of MnSOD, but not Cu/ZnSOD. The KO mice appeared normal and displayed comparable survivability and growth compared with wild type and SM-specific Cre control mice. Significantly increased nitrotyrosine levels were found in detrusor SM of SM-specific Sod2 KO mice compared with control mice, which was exacerbated after induction of diabetes by streptozotocin. No apparent structural changes were detected in the bladder of SM-specific Sod2 KO mice. However, these mice showed higher voiding frequency and voiding pressure, as well as shorter micturition intervals than control mice, suggesting that the increased OS may modulate detrusor contractility, resulting in bladder overactivity. CONCLUSIONS We successfully generated and characterized a mouse model with SM-specific deletion of Sod2, which can be used for exploring the mechanistic role of OS in SM-rich organs in different pathological conditions as well as evaluating the therapeutic interventions. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e239 Peer Review Report Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rania Elrashidy More articles by this author Guiming Liu More articles by this author Nan Xiao More articles by this author Michael Kavran More articles by this author Yexiang Huang More articles by this author Mingfang Tao More articles by this author Hoda Mohammad More articles by this author C Thomas Powell More articles by this author Firouz Daneshgari More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...