MP82-01 A GENETIC FEMALE MOUSE MODEL WITH CONGENITAL GENITOURINARY ANOMALIES AND URINARY INCONTINENCE

Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II1 Apr 2017MP82-01 A GENETIC FEMALE MOUSE MODEL WITH CONGENITAL GENITOURINARY ANOMALIES AND URINARY INCONTINENCE Akbari Pedram, Ali Fathollahi, Rong Mo, Michael Chua, Michael Kavran, Nicole Episalla, Chi-Chung Hui, Walid Farhat, and Adonis Hijaz Akbari PedramAkbari Pedram More articles by this author , Ali FathollahiAli Fathollahi More articles by this author , Rong MoRong Mo More articles by this author , Michael ChuaMichael Chua More articles by this author , Michael KavranMichael Kavran More articles by this author , Nicole EpisallaNicole Episalla More articles by this author , Chi-Chung HuiChi-Chung Hui More articles by this author , Walid FarhatWalid Farhat More articles by this author , and Adonis HijazAdonis Hijaz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2548AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Hedgehog signaling pathway is known to have important role in the urogenital development. Transcription mediators of the pathway, Gli2 and Gli3, have been shown to be heavily involved in proper urogenital sinus formation. Both Gli2 and Gli3 null mice are non-viable, and display severe urogenital ad hindgut malformations. Here, we have generated a compound genetic mutant, Gli2+/-;Gli3Δ699/+, that is viable well into adulthood, and displaying variable urogenital malformations including urinary incontinence in its females. We aim to characterize the urinary incontinence observed in Gli2+/-; Gli3Δ699/+ female mice and assess its functional, anatomical, and histological characteristics. METHODS Gli2+/- and Gli3Δ699/+ mice were crossed to generate the double mutant (Gli2+/-; Gli3Δ699/+) female mice and wild type female mice were used as comparison controls; which all were verified via Polymerase Chain Reactions. Void measurements, Cystometrogram (CMG) and leak point pressure (LPP) were performed in all genotypes to assess bladder functions. The mice were then sacrificed to harvest the bladders and urethras for gross characterization via ink injection and histological assays. Differences were reported as mean and standard errors of mean (SEM) and analyzed using univariate analysis. Statistical significance set at 0.05. RESULTS No significant differences between the mutant and wild type mice were detected for 24 hour urinary output [(n= 13) mean 26.5cc±5 vs ( n=7) mean 22.15cc±6, p=0.13]. CMG studies revealed a decrease in peak micturition pressure values and significantly reduced LPP in Gli2+/-; Gli3Δ699/+ mice compared to wild type mice [(n=5) 4.28 cmH2O±2.4 vs (n=4) 20.24 cmH2O±6.45, p<0.0001; (n=5) 6.66 cmH2O±1.6 vs (n=5) 26.5cmH2O±5, p<0.05; respectively]. Gross characterization revealed that the ano-genital distance was severely reduced in double mutant mice; however, the urethra, vagina, and anus all remain separate and distinctly identifiable in these mice. 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/+ female mice display persistent urinary incontinence with evident malformation of the bladder outlet and urethra. This presents a genetic mouse model for female urinary incontinence and alludes to potential genetic factors involved in the human condition. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1097 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Akbari Pedram More articles by this author Ali Fathollahi More articles by this author Rong Mo More articles by this author Michael Chua More articles by this author Michael Kavran More articles by this author Nicole Episalla More articles by this author Chi-Chung Hui More articles by this author Walid Farhat More articles by this author Adonis Hijaz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...