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

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 I 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. (C) 2009 Elsevier Inc. All rights reserved.