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J Pediatr Surg. 2009 Apr;44(4):759-66. doi: 10.1016/j.jpedsurg.2008.06.006.

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

Author information

  • 1Division of Pediatric Surgery and The Pediatric Surgery Laboratory, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Abstract

BACKGROUND/PURPOSE:

The study aimed to develop a mouse model of post-pullthrough Hirschsprung's disease that will allow investigation of mechanisms that cause postoperative complications.

METHODS:

We developed a novel microsurgical pullthrough operation on Balb/C mice and evaluated its effect on growth rate and stooling pattern. Histologic assessment of the pullthrough colon was performed. The pullthrough operation was then performed on Ednrb-/- mice that have aganglionic megacolon and Ednrb+/+ littermate controls, and the outcomes compared.

RESULTS:

The Balb/C pullthrough group had 97% survival at 1 week and 70% survival at 2 weeks. Body weight of the pullthrough animals declined 15% in the first week after surgery and subsequently normalized. The stooling pattern showed consistently softer stools in the pullthrough group, but no difference in frequency compared to controls. Histopathologic analyses 4 weeks postoperatively showed well-healed coloanal anastomoses. Two-week survival after pullthrough surgery in Ednrb-/- and Ednrb+/+ mice was 50.0%, and 69.2%, respectively (P = NS). Increased mortality in the Ednrb-/- mice was related to the technical challenge of performing microsurgery on smaller-sized mice with poor baseline health status.

CONCLUSIONS:

Our microsurgical pullthrough operation in mice is feasible and allows systematic investigations into potential mechanisms mediating post-pullthrough complications and poor long-term results in mouse models of Hirschsprung's disease.

PMID:
19361637
[PubMed - indexed for MEDLINE]
PMCID:
PMC4372194
Free PMC Article
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