Nerve growth factor (NGF), a target-derived neurotrophic molecule, is required specifically by sympathetic and dorsal root ganglion cells for their survival and maturation during embryonic and early postnatal development. In the present study, the NGF expression was studied both at the protein and mRNA level in normal and aganglionic intestines of Piebald-strain mice and also in 10 human specimens using immunohistochemical and reverse transcriptase polymerase chain reaction (RT-PCR) techniques. In the aganglionic intestines of the mice, immunoreactive NGF was found on the giant nerve fibers in the submucosal layer, but not found in the mucosal layer. In the mRNA study, the signal for NGFmRNA was less intense in the aganglionic rectum of the congenitally megacolonic mice than in the rectum of the normal mice. In contrast, the distal dilated colon of the congenitally megacolonic mice had a more intense signal for NGFmRNA than did the colon of normal mice. The results obtained from human specimens were compatible with the findings in the Piebald mice; the distal colons harvested from the patients with Hirschsprung's disease (or its allied disease) had a uniformly more intense signal for NGFmRNA than did the normal colons. The results of this study may indicate that NGF production is altered in the aganglionic intestines and also in the "transitional zone" in Hirschsprung's disease. The altered production of NGF may be useful in increasing the accuracy of diagnosis of Hirschsprung's disease.
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