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.
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.
Authors: Vincent C H Lui; William W C Cheng; Thomas Y Y Leon; Danny K C Lau; Maria-Mercedes Garcia-Barcelo; Maria-Mercedes Garcia-Bareclo; Xiao P Miao; Mandy K M Kam; Man T So; Yan Chen; Nancy A Wall; Mai H Sham; Paul K H Tam Journal: Gastroenterology Date: 2008-01-17 Impact factor: 22.682
Authors: Erik R Barthel; Allison L Speer; Daniel E Levin; Frédéric G Sala; Xiaogang Hou; Yasuhiro Torashima; Clarence M Wigfall; Tracy C Grikscheit Journal: J Vis Exp Date: 2012-12-01 Impact factor: 1.355
Authors: Alan J Burns; Allan M Goldstein; Donald F Newgreen; Lincon Stamp; Karl-Herbert Schäfer; Marco Metzger; Ryo Hotta; Heather M Young; Peter W Andrews; Nikhil Thapar; Jaime Belkind-Gerson; Nadege Bondurand; Joel C Bornstein; Wood Yee Chan; Kathryn Cheah; Michael D Gershon; Robert O Heuckeroth; Robert M W Hofstra; Lothar Just; Raj P Kapur; Sebastian K King; Conor J McCann; Nandor Nagy; Elly Ngan; Florian Obermayr; Vassilis Pachnis; Pankaj J Pasricha; Mai Har Sham; Paul Tam; Pieter Vanden Berghe Journal: Dev Biol Date: 2016-04-05 Impact factor: 3.582