title: Water avoidance stress results in an altered voiding phenotype in male mice.
abstract: OBJECTIVE
  We set out to characterize the voiding phenotypes of male mice to a water avoidance stress (WAS) protocol and compare the molecular changes with those induced by surgically induced partial bladder outlet obstruction (pBOO).
  
  
  METHODS
  Six-week-old male Swiss Webster mice housed with sibling littermates were individually placed on a platform centered in the middle of a water filled basin for 1 hr daily for 4 weeks. A non stressed cohort of sibling littermates served as controls. Measured end points included voiding frequency, voided volume, bladder mass, and in vivo cystometry. Molecular end points included myosin heavy chain (MHC) isoform distribution by PCR, and nuclear translocation of hypoxia inducible factor (HIF1α) and the nuclear factor of activated T-cells (NFAT) by gel shift assay. These molecular endpoints were compared with samples from male mice undergoing anatomic pBOO.
  
  
  RESULTS
  WAS resulted in increased average voided volumes and bladder mass, and a decrease in voiding frequency (P < 0.05). The slower MHC A isoform was only expressed in the pBOO group that developed severe hypertrophy. Gel shift assays revealed substantial increases in HIF1-α nuclear translocation in the group subjected to pBOO that developed severe hypertrophy but minimal changes in the pBOO group that developed minimal hypertrophy and the swim stress groups.
  
  
  CONCLUSIONS
  The WAS model induces moderate bladder wall hypertrophy in the absence of any surgical manipulation.
authors.affiliation: John W. Duckett Center for Pediatric Urology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: McGonagle
authors.forename: Ariana
authors.initials: A
authors.lastname: Smith
authors.forename: Stephan
authors.initials: S
authors.lastname: Butler
authors.forename: Joanna
authors.initials: J
authors.lastname: Sliwoski
authors.forename: Rita
authors.initials: R
authors.lastname: Valentino
authors.forename: Douglas
authors.initials: D
authors.lastname: Canning
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Zderic
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D006984:Hypertrophy; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D051379:Mice; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D013315:Stress, Psychological / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D013997:Time Factors; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001748:Urinary Bladder Neck Obstruction / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D014554:Urination; D014555:Urination Disorders / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D014563:Urodynamics; D014867:Water
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D050778:NFATC Transcription Factors; D014867:Water; D018995:Myosin Heavy Chains