title: Bladder function in mice with inducible smooth muscle-specific deletion of the manganese superoxide dismutase gene.
abstract: Manganese superoxide dismutase (MnSOD) is considered a critical component of the antioxidant systems that protect against oxidative damage. We are interested in the role of oxidative stress in bladder detrusor smooth muscle (SM) in different disease states. In this study, we generated an inducible, SM-specific Sod2(-/-) mouse model to investigate the effects of MnSOD depletion on the function of the bladder. We crossbred floxed Sod2 (Sod2(lox/lox)) mice with mice containing heterozygous knock-in of a gene encoding a tamoxifen-activated Cre recombinase in the SM22α promoter locus [SM-CreER(T2)(ki)(Cre/+)]. We obtained Sod2(lox/lox),SM-CreER(T2)(ki)(Cre/+) mice and injected 8-wk-old males with 4-hydroxytamoxifen to induce Cre-mediated excision of the floxed Sod2 allele. Twelve weeks later, SM-specific deletion of Sod2 and depletion of MnSOD were confirmed by polymerase chain reaction, immunoblotting, and immunohistochemistry. SM-specific Sod2(-/-) mice exhibited normal growth with no gross abnormalities. A significant increase in nitrotyrosine concentration was found in bladder SM tissue of SM-specific Sod2(-/-) mice compared with both wild-type mice and Sod2(+/+), SM-CreER(T2)(ki)(Cre/+) mice treated with 4-hydroxytamoxifen. Assessment of 24-h micturition in SM-specific Sod2(-/-) mice revealed significantly higher voiding frequency compared with both wild-type and SM-specific Cre controls. Conscious cystometry revealed significantly shorter intercontraction intervals and lower functional bladder capacity in SM-specific Sod2(-/-) mice compared with wild-type mice. This novel model can be used for exploring the mechanistic role of oxidative stress in organs rich in SM in different pathological conditions.
authors.affiliation: Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio;
authors.forename: Guiming
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio; Faculty of Pharmacy, Biochemistry Department, Zagazig University, Zagazig, Egypt;
authors.forename: Rania A
authors.initials: RA
authors.lastname: Elrashidy
authors.affiliation: Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio; Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China; and.
authors.forename: Nan
authors.initials: N
authors.lastname: Xiao
authors.affiliation: Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio;
authors.forename: Michael
authors.initials: M
authors.lastname: Kavran
authors.affiliation: Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio; Department of Urology, The First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Yexiang
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio;
authors.forename: Mingfang
authors.initials: M
authors.lastname: Tao
authors.affiliation: Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio;
authors.forename: C Thomas
authors.initials: CT
authors.lastname: Powell
authors.affiliation: Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio;
authors.forename: Edward
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio;
authors.forename: Ghazal
authors.initials: G
authors.lastname: Sadeghi
authors.affiliation: Faculty of Pharmacy, Biochemistry Department, Zagazig University, Zagazig, Egypt;
authors.forename: Hoda E
authors.initials: HE
authors.lastname: Mohamed
authors.affiliation: Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio; firouz.daneshgari@case.edu.
authors.forename: Firouz
authors.initials: F
authors.lastname: Daneshgari
mesh_terms: D000818:Animals; D017353:Gene Deletion; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000201:enzymology*; D018384:Oxidative Stress / Q000502:physiology; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics*; D001743:Urinary Bladder / Q000201:enzymology*; D000099156:Superoxide Dismutase 2
chemical_list: D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2
keywords: inducible cre-loxp recombination; oxidative stress