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Related Experiment Video

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A Mouse Model of Intestinal Partial Obstruction
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Mouse model of endoscopically ablated enteric nervous system.

Hassan A Khalil1, Masae Kobayashi1, Puneet Rana1

  • 1Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, California.

The Journal of Surgical Research
|August 25, 2015
PubMed
Summary

Researchers created a new mouse model for Hirschsprung disease by chemically ablating the enteric nervous system using colonoscopy. This model aids in testing new therapies for the condition.

Keywords:
AganglionosisChemically ablated enteric nervous systemHirschsprung diseaseMiniature endoscopyMouse model

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Area of Science:

  • Gastroenterology
  • Developmental Biology
  • Surgical Innovation

Background:

  • Existing transgenic models for Hirschsprung disease have limitations in survival and require specialized diets.
  • A novel approach is needed to create more accessible and effective animal models for Hirschsprung disease research.

Purpose of the Study:

  • To develop a new, chemically induced animal model of Hirschsprung disease using small animal colonoscopy.
  • To evaluate the efficacy of benzalkonium chloride (BAC) in ablating the enteric nervous system in mice.

Main Methods:

  • Adult C57BL/6 mice underwent colonoscopy with submucosal injections of varying concentrations of benzalkonium chloride (BAC) in the distal colon and rectum.
  • Injection sites were analyzed histologically and via immunostaining for β-tubulin III at 7 and 28 days post-procedure.
  • Different concentrations of BAC and multiple injections were tested for efficacy and tolerance.

Main Results:

  • Submucosal injection of 0.02% BAC effectively ablated 82% of myenteric ganglia, causing megacolon, a condition sustained up to 28 days.
  • Lower concentrations of BAC showed minimal impact on the myenteric neuronal network.
  • Multiple injections of 0.002% or 0.02% BAC were tolerated, while 0.2% BAC caused acute toxicity.

Conclusions:

  • A novel, chemically induced model of enteric nervous system ablation in the mouse colon and rectum was successfully established.
  • This model offers a valuable platform for evaluating targeted cell delivery therapies for Hirschsprung disease.
  • The colonoscopic delivery method provides a reproducible and potentially less invasive approach to creating disease models.