A genetic female mouse model with congenital genitourinary anomalies and adult stages of urinary incontinence

• Published in: Neurourology and urodynamics Vol. 36; no. 8; pp. 1981 - 1987
• Main Authors: Akbari, Pedram, Fathollahi, Ali, Mo, Rong, Kavran, Michael, Episalla, Nicole, Hui, Chi‐Chung, Farhat, Walid A., Hijaz, Adonis K.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2017
• Subjects: Animals; Bladder; Disease Models, Animal; Female; female urinary incontinence; Gene Expression Regulation, Developmental; Genetic factors; Gli transcription factors; Mice; mouse model; Mucosa; Nerve Tissue Proteins - genetics; Pressure; Rodents; Signal Transduction - physiology; Smooth muscle; smooth muscle development; Urethra; Urinary bladder; Urinary incontinence; Urinary Incontinence - genetics; Urination; Urogenital Abnormalities - genetics; Zinc Finger Protein Gli2 - genetics; Zinc Finger Protein Gli3 - genetics; female urinary incontinence; smooth muscle development; mouse model; Gli transcription factors
• ISSN: 0733-2467; 1520-6777
• DOI: 10.1002/nau.23230

AIMS To characterize the urinary incontinence observed in adult Gli2+/−; Gli3Δ699/+ female mice and identify the defects underlying the condition. METHODS Gli2+/− and Gli3Δ699/+ mice were crossed to generate: wild‐type, mutant Gli2 (Gli2+/−), mutant Gli3 (Gli3Δ699/+), and double mutant (Gli2+/−; Gli3Δ699/+) 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+/−; Gli3Δ699/+ bladders. LPP were significantly reduced in Gli2+/−; Gli3Δ699/+ mice compared to wild‐type mice. CMG studies revealed a decrease in peak micturition pressure values in Gli2+/−; Gli3Δ699/+ mice compared with all other groups. No significant differences between mutant and wild‐type mice were detected in urinary output. Histological analyses revealed Gli2+/−; Gli3Δ699/+ 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+/−; Gli3Δ699/+ 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.