title: Attenuation of bladder overactivity in KIT mutant rats.
abstract: OBJECTIVE
  To investigate morphological and physiological findings in the bladder of KIT mutant (WsRCWs/Ws) rats to clarify whether the disturbance of KIT pathways affects bladder activity. To discuss the potential role of KIT-positive interstitial cells of Cajal (ICC)-like cells in the urinary bladder.
  
  
  METHODS
  Reverse transcriptase-polymerase chain reaction and western blotting was used to confirm the absence of c-kit mRNA and protein in the bladders of 12-week-old WsRCWs/Ws rats. Light and transmission electron microscopy was used to identify the differences in morphological and ultrastructural characteristics of the bladder between WsRCWs/Ws and wild-type (WsRC+/+) rats. The voiding pattern of WsRCWs/Ws rats and the effects of cyclophosphamide (CYP) and protamine sulphate on bladder function were examined using cystometry.
  
  
  RESULTS
  In WsRC+/+ rats, c-kit mRNA and KIT protein expression were observed in the urinary bladder, while they were not detectable in WsRCWs/Ws rats. Deformation of ICC-like cells with the collapse of the organelle was not observed in the bladders of WsRCWs/Ws rats. Each cystometry variable in WsRCWs/Ws rats was similar to that in WsRC+/+ rats. The reduction in the intercontraction intervals in WsRCWs/Ws rats with chemically (CYP and protamine sulphate) induced cystitis was significantly lower than in WsRC+/+ rats (P < 0.05).
  
  
  CONCLUSIONS
  Certain voiding disturbances might be associated with impaired KIT signalling in ICC-like cells, therefore, KIT could be a candidate target for medical therapy in the future.
authors.affiliation: Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Okada
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kojima
authors.forename: Yasue
authors.initials: Y
authors.lastname: Kubota
authors.forename: Kentaro
authors.initials: K
authors.lastname: Mizuno
authors.forename: Shoichi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003520:Cyclophosphamide / Q000494:pharmacology; D003556:Cystitis / Q000139:chemically induced; D006494:Heparin Antagonists / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D056885:Interstitial Cells of Cajal / Q000378:metabolism; D008407:Mast Cells / Q000737:chemistry; D008854:Microscopy, Electron; D011479:Protamines / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000737:chemistry; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053201:Urinary Bladder, Overactive / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D006494:Heparin Antagonists; D007166:Immunosuppressive Agents; D011479:Protamines; D003520:Cyclophosphamide; D019009:Proto-Oncogene Proteins c-kit