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Updated: Jun 19, 2026
Immunostaining to Visualize Murine Enteric Nervous System Development
Published on: April 29, 2015
Muscarinic cholinergic receptors in the piebald mouse model for Hirschsprung's disease
Abstract:
The contracted segment of terminal large intestine in both Hirschsprung's disease in humans and in the piebald-lethal strain of mice with congenital megacolon may result from muscarinic cholinergic receptor denervation supersensitivity. This hypothesis was tested by direct binding studies using the muscarinic receptor ligand, tritiated quinuclidinyl benzilate. There were no differences in either the receptor density, dissociation constant, or agonist/antagonist Hill coefficients in the proximal, middle, or distal colon of mice with congenital megacolon as compared with normal littermates. These data do not support the concept of denervation supersensitivity. The data support the suggestion that absence of the inhibitory neurons of the enteric nervous system accounts for the hyperexcitability of the musculature of the aganglionic terminal segment and the obstructive constriction of the segment.
Insights
This study investigated Hirschsprung's disease and congenital megacolon in mice. The findings do not support denervation supersensitivity but suggest absent inhibitory neurons cause aganglionic segment hyperexcitability and constriction.
Area of Science:
- Gastroenterology
- Neuroscience
- Developmental Biology
Background:
- Hirschsprung's disease and congenital megacolon involve a contracted terminal large intestine.
- A hypothesis suggested muscarinic cholinergic receptor denervation supersensitivity as a cause.
Purpose of the Study:
- To test the hypothesis of denervation supersensitivity in the aganglionic colon.
- To investigate the role of enteric nervous system neurons in congenital megacolon.
Main Methods:
- Direct binding studies using tritiated quinuclidinyl benzilate, a muscarinic receptor ligand.
- Comparison of receptor density, dissociation constant, and Hill coefficients in normal and congenital megacolon mice.
Main Results:
- No significant differences were found in muscarinic receptor parameters between normal and affected mice.
- The data do not support the denervation supersensitivity theory.
Conclusions:
- Absence of inhibitory neurons in the enteric nervous system likely causes aganglionic segment hyperexcitability.
- This neuronal absence leads to the obstructive constriction observed in congenital megacolon.
