Anorectal malformations associated with enteric dysganglionosis in Danforth's short tail (Sd) mice

Background: The spontaneous mutant Danforth's short tail (Sd) mouse has bee n studied over the last 60 years from the morphological, embryological, and genetic point of view. The Sd mutation affects a gene essential to notocho rdal development,and the Sd mouse phenotype represents an analogue of human caudal regression syndrome. The Sd/Sd mouse presents different types of an orectal malformations (ARM) and was suggested as a simple and cheap model o f investigation of ARM morphology and embryology. In the current study, the Sd mouse enteric nervous system (ENS) was thoroughly investigated with spe cific immunohistochemical markers. Methods: Macroscopic analysis,normal histology, and immunohistochemical tec hniques for detecting neurofilaments (NF) and NOS1 were used to study ENS o f 138 Sd mice and 25 controls. Results: The surprising results of this study showed that Sd mutation is as sociated with different degrees of hypoganglionosis and aganglionosis. In 4 1% of Sd/SD-affected mice, the rectal pouch was aganglionic and in the rema ining 58% was severely hypoganglionic. In addition, 4.1% of heterozygous mi ce presented a distal aganglionosis and 8.3% hypoganglionosis. Conclusions: These results suggest that Sd mutation independently affects d istinct cell lines during early organogenesis, as notochord cells, ventral hingut endoderm, and neuroblasts migrating from neural crest cells. Compari ng the Sd murine model with human pathology, this study confirms that the a ssociation between ARM and intestinal dysganglionosis is not rare and under lines the importance of detecting in every ARM patient the innervation abno rmalities of rectal pouch and fistulas. J Pediatr Surg 34:1818-1821. Copyri ght (C) 1999 by W.B. Saunders Company.