Selective depletion of substance P-immunoreactive neurones in the transitional zone of the colon in piebald lethal mice.

The distribution of substance P in the colon of piebald lethal (s(1)/s(1)) mice was studied by radioimmunoassay and immunohistochemistry. These animals inherit as a Mendelian recessive trait an aganglionic distal colon. In the region proximal to the aganglionic segment, there is an extensive transitional or hypoganglionic zone, in which the total number of nerve cells in the myenteric plexus is reduced, while those in the submucous plexus tend to be normal. Immunohistochemical studies indicate that substance P-immunoreactive neurones accounted for approx. 10% of the total number of normal myenteric neurones, but in the hypoganglionic region they accounted for about 5%, and this difference was statistically significant. By radioimmunoassay, the concentrations of substance P in both the aganglionic and the hypoganglionic regions of the colon were reduced compared with the corresponding segments in normal mice. However calculation of the mean substance P content per neurone revealed similar quantities (about 1 fmol) in both normal and s(1)/s(1) mice. Substance P-immunoreactivity in the tissue extracts eluted in the same position as the synthetic peptide on ion exchange and gel filtration chromatography. It is suggested that a sub-population of substance P-immunoreactive neurones in the hypoganglionic zone is selectively depleted compared with other myenteric neurones. The factors involved remain to be elucidated, but this strain of mice could prove useful for studies of the mechanisms involved in differentiation and development of enteric peptidergic neurones.