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GDNF deficit in Hirschsprung's disease
G Martucciello1, H Thompson, C Mazzola
1Department and Chair of Pediatric Surgery, Giannina Gaslini Children's Hospital, University of Genoa, Italy.
Journal of Pediatric Surgery
|February 24, 1998
Summary
Glial cell line-derived neurotrophic factor (GDNF) expression is reduced in Hirschsprung disease (HD) patients lacking GDNF gene mutations. This deficit in GDNF signaling contributes to the pathogenesis of HD.
Area of Science:
- Gastroenterology
- Neuroscience
- Developmental Biology
Background:
- Glial cell line-derived neurotrophic factor (GDNF) is a ligand for the RET receptor.
- GDNF and RET mutations are linked to Hirschsprung disease (HD).
- GDNF mutations alone are not sufficient to cause HD.
Purpose of the Study:
- Investigate GDNF expression in the enteric nervous system of HD patients without GDNF gene mutations.
- Determine if a GDNF expression deficit contributes to HD pathogenesis.
Main Methods:
- Immunohistochemistry using rabbit polyclonal antibodies against human GDNF.
- Analysis of surgical specimens from 30 HD cases and 10 controls.
- Histochemical and immunohistochemical staining for various neural and glial markers.
Main Results:
- High GDNF expression observed in normal intestine and HD ganglionic segments.
- Absence of GDNF expression in the aganglionic segment of HD patients.
- Reduced GDNF immunoreactivity in the hypoganglionic segment of HD patients.
Conclusions:
- GDNF is crucial for enteric neuron survival and function.
- GDNF expression deficits, alongside gene mutations, disrupt GDNF/Ret signaling.
- These disruptions contribute significantly to the development of Hirschsprung disease.