A genetic female mouse model with congenital genitourinary anomalies and adult stages of urinary incontinence. Issue 8 (28th February 2017)

• Record Type: Journal Article
• Authors: Akbari, Pedram; Fathollahi, Ali; Mo, Rong; Kavran, Michael; Episalla, Nicole; Hui, Chi‐Chung; Farhat, Walid A.; Hijaz, Adonis K.
• Is Part Of: Neurourology and urodynamics. Volume 36:Issue 8(2017:Nov.)
• Page Start: 1981
• Page End: 1987
• Publication Date: 2017-02-28
• Subjects: female urinary incontinence -- Gli transcription factors -- mouse model -- smooth muscle development; Urinary organs -- Periodicals; Urodynamics -- Periodicals; Urology -- Periodicals; 616.6
• DOI: 10.1002/nau.23230
• Languages: English
• ISSNs: 0733-2467

Abstract

Abstract : AIMS: To characterize the urinary incontinence observed in adult Gli2 +/ − ; Gli3 Δ699/+ female mice and identify the defects underlying the condition. METHODS: Gli2 +/ − and Gli3 Δ699/+ mice were crossed to generate: wild‐type, mutant Gli2 ( Gli2 +/− ), mutant Gli3 ( Gli3 Δ699/+ ), and double mutant ( Gli2 +/− ; Gli3 Δ699/+ ) female mice, verified via Polymerase Chain Reactions. Bladder functional studies including cystometrogram (CMG), leak point pressure (LPP), and voiding testing were performed on adult female mice. Female bladders and urethras were also analyzed via ink injection and histological assays. RESULTS: CMG tracing showed no signal corresponding to the filling of the Gli2 +/− ; Gli3 Δ699/+ bladders. LPP were significantly reduced in Gli2 +/− ; Gli3 Δ699/+ mice compared to wild‐type mice. CMG studies revealed a decrease in peak micturition pressure values in Gli2 +/− ; Gli3 Δ699/+ mice compared with all other groups. No significant differences between mutant and wild‐type mice were detected in urinary output. Histological analyses revealed Gli2 +/− ; Gli3 Δ699/+ mice exhibited a widened urethra and a decrease in smooth muscle layer thickness in the bladder outlet and urethra, with increased mucosal folding. CONCLUSIONS: Gli2 +/ − ; Gli3 Δ699/+ adult female mice display persistent urinary incontinence due to the malformation of the bladder outlet and urethra. This presents a consistent and reliable genetic mouse model for female urinary incontinence and alludes to the key role of genetic factors involved in the condition.