Intestinal neuronal dysplasia-like pathology in Ncx/Hox11L.1 gene-deficient mice

Background/Purpose: Ncx/Hox11L.1-deficient (Ncx-/-) mice specifically creat ed by the authors had mega-ileo-ceco-colon (mega-ICC) with a caliber change in the proximal colon. The authors studied the nerve distribution in the b owel of these Ncx-/- mice to determine the cause of their bowel dysmotility . Methods: Four-week-old Ncx-/- mice (n = 10; 5 with mega-ICC, 5 without mega -ICC) were killed and the bowel harvested. Half of each specimen was snap f rozen for AchE and NADPH-dia pho rase histochemistry, and the other half we re fixed with 10% formalin for H&E staining and immunohistochemistry using PGP9.5 antibody (a marker for neurons), C-kit antibody (a marker for intest inal pacemaker cells), and stem cell factor antibody (a marker for C-kit li gand). Age-matched wild-type normal mice (n = 5) served as controls. Results: In the ileum, cecum, and proximal colon from all Ncx-/- mice (irre spective of the association of mega-ICC), typical findings of human intesti nal neuronal dysplasia (IND) ia, obvious hyperganglionosis in neuronal plex uses on PGP9.5 immunohistochemistry, ectopic ganglia in the mucosal and mus cular layers on AchE histochemistry, and ghost-like ganglia on NADPH-diapho rase histochemistry were found. Likewise, in normal caliber distal colon fr om these mice, the distribution of ganglion cells, C-kit, and stem cell fac tor was normal. In control specimens, there was no ectopic ganglia or hyper ganglionosis. Conclusions: These findings suggest that the Ncx/Hox11L.1 gene is required for the proper innervation of the enteric nervous system in mice, and our d eficient strain may be useful as a model for studying IND in humans. J Pedi atr Surg 36:1293-1296. Copyright (C) 2001 by W.B. Saunders Company.