title: Mouse model of endoscopically ablated enteric nervous system.
abstract: BACKGROUND
  Current transgenic animal models of Hirschsprung disease are restricted by limited survival and need for special dietary care. We used small animal colonoscopy to produce chemically ablated enteric nervous system in the distal colon and rectum of normal mice.
  
  
  METHODS
  Adult C57BL/6 mice underwent colonoscopy with submucosal injection of 75-100 μL of saline (n = 2) or 0.002% (n = 2), 0.02% (n = 15), or 0.2% (n = 2) benzalkonium chloride (BAC). Each mouse received 1-3 injections in the distal colon and rectum. Mice were sacrificed on postprocedure day 7 or 28. Injection sites were analyzed histologically and with immunostaining for β-tubulin III.
  
  
  RESULTS
  Submucosal injection of 0.02% BAC resulted in megacolon and obliteration of 82 ± 8.8% of myenteric ganglia at the injection site on postprocedure day 7 compared with normal colon. This effect was sustained until day 28. Injection of 0.002% BAC had little effect on the myenteric neuronal network at these time points. Multiple injections of 0.002% or 0.02% BAC (up to three injections per mouse) were well tolerated. Injection of 0.2% BAC caused acute toxicity or death.
  
  
  CONCLUSIONS
  A novel model of chemically ablated enteric nervous system in the mouse colon and rectum is introduced. This model can be valuable in evaluating targeted cell delivery therapies for Hirschsprung disease.
authors: Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, California.
authors: Hassan A
authors: HA
authors: Khalil
authors: Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, California.
authors: Masae
authors: M
authors: Kobayashi
authors: Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, California.
authors: Puneet
authors: P
authors: Rana
authors: Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, California.
authors: Justin P
authors: JP
authors: Wagner
authors: Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, California.
authors: Andrew
authors: A
authors: Scott
authors: Department of Surgery, Tufts Medical Center, Boston, Massachusetts.
authors: James
authors: J
authors: Yoo
authors: Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, California. Electronic address: jdunn@mednet.ucla.edu.
authors: James C Y
authors: JC
authors: Dunn
mesh_terms: D055011:Ablation Techniques / Q000379:methods*; D000818:Animals; D001548:Benzalkonium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000473:pathology; D003113:Colonoscopy; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006627:Hirschsprung Disease; D007267:Injections; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000294:innervation / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012007:Rectum / Q000187:drug effects / Q000294:innervation / Q000473:pathology
chemical_list: D001548:Benzalkonium Compounds
keywords: Aganglionosis; Chemically ablated enteric nervous system; Hirschsprung disease; Miniature endoscopy; Mouse model