Alimentary TractDevelopment of interstitial cells of Cajal and pacemaking in mice lacking enteric nerves☆,☆☆
Section snippets
Animals
GDNF knockout mice (D0) were obtained from the Laboratory of Mammalian Genes and Development at the National Institutes of Child Health and Human Development (Bethesda, MD) from FVB/B6/129 as described previously.24 The null mutation is a lethal knockout, and the mice die shortly after birth. Therefore, each litter was removed immediately after birth and killed by chloroform inhalation and exsanguinated by decapitation after cervical dislocation. The GI tract from the proximal esophagus to
Morphological studies
Stomachs, jejunums, and colons from 81 animals were examined for the presence of enteric neurons using immunohistochemical and histochemical techniques. The pan-neuronal marker PGP 9.5 was used to determine the distribution of enteric neurons and processes. In wild-type (+/+) and heterozygous (+/−) tissues, antibodies to PGP 9.5 detected intense immunoreactivity in myenteric neurons and in interganglionic nerve bundles throughout the gastric antrum, small intestine, and colon (Figure 1A).
Discussion
Many investigators have described electrical rhythmicity in the GI tract as non-neural in origin (for review, see Szurszewski30). This conclusion was based on the observation that treatment of the gut with tetrodotoxin, to block propagation of nerve action potentials, does not eliminate slow wave activity. The present study provides powerful support to the notion that electrical rhythmicity in the GI tract is not dependent on inputs from enteric neurons and shows that development and
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Address requests for reprints to: Sean M. Ward, Ph.D., Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557. e-mail: [email protected]; fax: (775) 784-6903.
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Supported by National Institutes of Health grant DK40569. The Morphology Core Laboratory (supported by DK41315) was used for the immunohistochemical studies.