A novel corrective pullthrough surgery in a mouse model of Hirschsprung's disease

Area of Science:

• Surgical innovation in animal models
• Gastrointestinal surgery
• Pediatric surgery research

Background:

• Hirschsprung's disease is a congenital condition characterized by aganglionic megacolon.
• Postoperative complications following pullthrough surgery are a significant clinical challenge.
• Existing mouse models do not adequately replicate these complex postoperative issues.

Purpose of the Study:

• To develop a novel microsurgical pullthrough operation in mice.
• To establish a reproducible animal model for studying post-pullthrough Hirschsprung's disease complications.
• To investigate the underlying mechanisms contributing to poor outcomes after surgery.

Main Methods:

• A novel microsurgical pullthrough operation was performed on Balb/C mice.
• Evaluation included growth rate, stooling patterns, and histopathologic assessment of the colon.
• The procedure was subsequently performed on Ednrb-/- (aganglionic) and Ednrb+/+ (control) mice.

Main Results:

• Balb/C mice showed 70% survival at 2 weeks post-surgery, with temporary weight loss and softer stools.
• Histopathology confirmed well-healed coloanal anastomoses at 4 weeks.
• Survival in Ednrb-/- and Ednrb+/+ mice was 50% and 69.2%, respectively; higher mortality in Ednrb-/- mice was attributed to surgical challenges.

Conclusions:

• The developed microsurgical pullthrough operation is feasible in mice.
• This technique provides a viable platform for systematic investigation of post-pullthrough complications.
• The model facilitates research into mechanisms underlying poor long-term results in Hirschsprung's disease models.