title: Functional and morphologic characterizations of the diabetic mouse corpus cavernosum: comparison of a multiple low-dose and a single high-dose streptozotocin protocols.
abstract: BACKGROUND
  With the advent of genetically modified mice, it seems particularly advantageous to develop a mouse model of diabetic erectile dysfunction.
  
  
  OBJECTIVE
  To establish a mouse model of type I diabetes by implementation of either multiple low-dose streptozotocin (STZ) protocol or single high-dose STZ protocol and to evaluate morphologic alterations in the cavernous tissue and subsequent derangements in penile hemodynamics in vivo.
  
  
  METHODS
  Eight-week-old C57BL/6J mice were divided into three groups: a control group, a group administered the multiple low-dose STZ protocol (50 mg/kg x 5 days), and a group administered the single high-dose STZ protocol (200 mg/kg).
  
  
  METHODS
  After 8 weeks, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was then harvested and stained with hydroethidine (in situ analysis of superoxide anion), TUNEL, or antibodies to nitrotyrosine (marker of peroxynitrite formation), PECAM-1, smooth muscle alpha-actin, and phospho-eNOS. Penis specimens from a separate group of animals were used for phospho-eNOS and eNOS western blot or cGMP determination.
  
  
  RESULTS
  Erectile function was significantly less in diabetic groups than in control group. The generation of superoxide anion and nitrotyrosine and the number of apoptotic cells in both cavernous endothelial and smooth muscle cells were significantly higher in diabetic groups than in control group. Cavernous tissue phospho-eNOS and cGMP expression and the number of endothelial and smooth muscle cells were lower in diabetic groups than in control group. Both diabetic models resulted in similar structural and functional derangements in the corpus cavernosum; however, the mortality rate was higher in mice receiving single high-dose of STZ than in those receiving multiple low-doses.
  
  
  CONCLUSIONS
  The mouse model of type I diabetes is useful and technically feasible for the study of the pathophysiologic mechanisms involved in diabetic erectile dysfunction.
authors.affiliation: National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea.
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Jin
authors.forename: Woo Jean
authors.initials: WJ
authors.lastname: Kim
authors.forename: Jae Sook
authors.initials: JS
authors.lastname: Song
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Choi
authors.forename: Shuguang
authors.initials: S
authors.lastname: Piao
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Shin
authors.forename: Munkhbayar
authors.initials: M
authors.lastname: Tumurbaatar
authors.forename: Buyankhuu
authors.initials: B
authors.lastname: Tuvshintur
authors.forename: Moon-Suk
authors.initials: MS
authors.lastname: Nam
authors.forename: Ji-Kan
authors.initials: JK
authors.lastname: Ryu
authors.forename: Jun-Kyu
authors.initials: JK
authors.lastname: Suh
mesh_terms: D000818:Animals; D002985:Clinical Protocols; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003922:Diabetes Mellitus, Type 1; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007172:Erectile Dysfunction / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D005240:Feasibility Studies; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D010413:Penis / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology*; D013311:Streptozocin / Q000008:administration & dosage
chemical_list: D013311:Streptozocin