title: A genetic female mouse model with congenital genitourinary anomalies and adult stages of urinary incontinence.
abstract: OBJECTIVE
  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.
authors.affiliation: Program in Developmental & Stem Cell Biology, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Pedram
authors.initials: P
authors.lastname: Akbari
authors.affiliation: New York Medical College, New York, New York.
authors.forename: Ali
authors.initials: A
authors.lastname: Fathollahi
authors.affiliation: Program in Developmental & Stem Cell Biology, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Rong
authors.initials: R
authors.lastname: Mo
authors.affiliation: Department of Radiology, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Michael
authors.initials: M
authors.lastname: Kavran
authors.affiliation: Georgetown University School of Medicine, Washington, DC, Washington.
authors.forename: Nicole
authors.initials: N
authors.lastname: Episalla
authors.affiliation: Program in Developmental & Stem Cell Biology, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Hui
authors.affiliation: Program in Developmental & Stem Cell Biology, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.|Division of Urology, Department of Surgery, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Walid A
authors.initials: WA
authors.lastname: Farhat
authors.affiliation: University Hospitals Cleveland Medical Center, Urology Institute, Cleveland, Ohio.
authors.forename: Adonis K
authors.initials: AK
authors.lastname: Hijaz
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D014549:Urinary Incontinence / Q000235:genetics*; D014564:Urogenital Abnormalities / Q000235:genetics*; D000075746:Zinc Finger Protein Gli2 / Q000235:genetics*; D000074290:Zinc Finger Protein Gli3 / Q000235:genetics*
chemical_list: C465571:Gli3 protein, mouse; D009419:Nerve Tissue Proteins; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
keywords: Gli transcription factors; female urinary incontinence; mouse model; smooth muscle development