Akbari Pedram, Fathollahi Ali, Mo Rong, Kavran Michael, Episalla Nicole, Hui Chi-Chung, Farhat Walid A, Hijaz Adonis K
Program in Developmental & Stem Cell Biology, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
New York Medical College, New York, New York.
Neurourol Urodyn. 2017 Nov;36(8):1981-1987. doi: 10.1002/nau.23230. Epub 2017 Feb 28.
To characterize the urinary incontinence observed in adult Gli2 ; Gli3 female mice and identify the defects underlying the condition.
Gli2 and Gli3 mice were crossed to generate: wild-type, mutant Gli2 (Gli2 ), mutant Gli3 (Gli3 ), and double mutant (Gli2 ; Gli3 ) 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.
CMG tracing showed no signal corresponding to the filling of the Gli2 ; Gli3 bladders. LPP were significantly reduced in Gli2 ; Gli3 mice compared to wild-type mice. CMG studies revealed a decrease in peak micturition pressure values in Gli2 ; Gli3 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 mice exhibited a widened urethra and a decrease in smooth muscle layer thickness in the bladder outlet and urethra, with increased mucosal folding.
Gli2 ; Gli3 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.
描述成年Gli2；Gli3雌性小鼠中观察到的尿失禁情况，并确定该病症的潜在缺陷。
将Gli2和Gli3小鼠进行杂交，以产生野生型、突变型Gli2（Gli2）、突变型Gli3（Gli3）和双突变型（Gli2；Gli3）雌性小鼠，并通过聚合酶链反应进行验证。对成年雌性小鼠进行膀胱功能研究，包括膀胱压力容积测定（CMG）、漏点压力（LPP）和排尿测试。还通过墨水注射和组织学分析对雌性膀胱和尿道进行了分析。
CMG追踪显示，Gli2；Gli3膀胱充盈时无相应信号。与野生型小鼠相比，Gli2；Gli3小鼠的LPP显著降低。CMG研究显示，与所有其他组相比，Gli2；Gli3小鼠的排尿峰值压力值降低。突变型和野生型小鼠的尿量无显著差异。组织学分析显示，Gli2；Gli3小鼠的尿道增宽，膀胱出口和尿道的平滑肌层厚度降低，黏膜褶皱增加。
Gli2；Gli3成年雌性小鼠因膀胱出口和尿道畸形而表现出持续性尿失禁。这为女性尿失禁提供了一个一致且可靠的遗传小鼠模型，并暗示了遗传因素在该病症中的关键作用。
