Bladder function in mice with inducible smooth muscle-specific deletion of the
manganese superoxide dismutase gene.
Authors Liu G, Elrashidy RA, Xiao N, Kavran M, Huang Y, Tao M, Powell CT, Kim E, Sadeghi
G, Mohamed HE, Daneshgari F
Submitted By Submitted Externally on 10/26/2015
Status Published
Journal American journal of physiology. Cell physiology
Year 2015
Date Published 8/1/2015
Volume : Pages 309 : C169 - 78
PubMed Reference 25948732
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 SM22a 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.

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