Abstract
Hirschsprung's disease is characterized by aganglionosis of the distal colon and hypertonicity of the anal sphincter. Endothelin receptor type B mutant (piebald) mice phenotypically resemble infants with Hirschsprung's disease in that these mice are susceptible to developing toxic megacolon because of the absence of ganglion cells in their distal colon. Therefore, we hypothesized that newborn piebald mice would have a higher resting anal sphincter pressure than would newborn wild-type mice. To test this hypothesis, we developed a reliable and reproducible technique for measuring the resting anal sphincter pressure in mice. Heterozygote breeding pairs of endothelin receptor type B mutant mice were purchased and bred in our animal facility. Pregnant, time-dated C57BL/6J mice provided control newborn mice. One-day-old newborn mice were evaluated for resting anal sphincter pressure. Under the operating microscope, a 24-gauge open-tip epidural catheter was placed into the anus until a deflection (approximately 3 to 5 mm) was noticed on a polygraph pressure monitor. Three consecutive measurements were obtained for each mouse. Mean values for each group were determined and compared using Student's t test. The resting anal sphincter pressure (mean +/- standard deviation) in newborn C57BL/6J mice was 13.3 +/- 2.6 mmHg, whereas that in piebald mice 22.7 +/- 2.5 mmHg (P < 0.0001). Therefore, because of their increased resting anal sphincter pressure, piebald mice may provide a useful animal model for the study of Hirschsprung's disease.
