Selective chemical ablation of the enteric plexus in mice

Although genetically aganglionic mice such as piebald lethal and lethal spotted mice exhibit striking similarities to the human condition of Hirschsprung's disease (HD), the aganglionic segment is very short and always located in the distal part of the rectum. Topical application of benzalkonium chloride (BAC) to the rectum of rats has been reported to result in segmental aganglionosis. To induce chemical ablation of the enteric plexus in mice to produce an aperistaltic narrow segment simulating HD, 32 mice were divided into three groups: (1) abdominal (n=12), for sigmoid colon treatment; (2) rectal (n=10), for rectum treatment; and (3) controls (n=10). For groups 1 and 2, 0.1% BAC was applied to a 1-cm serosal surface of the bowel for 15 min. In the controls, isotonic saline was applied in this fashion. A detailed histologic examination was performed using hematoxylin and eosin staining and acetylcholinesterase histochemistry. Ten animals (9 in group 1 and 1 in group 2) died 1 to 9 weeks after BAC treatment. Autopsy revealed a narrow segment of bowel at the site of BAC treatment and marked dilatation of the bowel proximal to the narrow segment. The remaining animals were killed 12 weeks after BAC treatment. Histologic examination demonstrated normal myenteric and submucous plexuses in the controls, whereas there was a total lack of innervation in the BAC-treated segments.Topical application of BAC thus successfully produced a narrow aganglionic segment of bowel in normal mice. This model provides the basis for future studies to investigate the pathophysiology of HD and megacolon and for comparison with genetically aganglionic mice.