NDLI: Alimentary tract innervation deficits and dysfunction in mice lacking GDNF family receptor α2

Content Provider	PubMed Central
Author	Rossi, Jari Herzig, Karl-heinz Võikar, Vootele Hiltunen, Päivi H. Mikael, Segerstråle Airaksinen, Matti S.
Copyright Year	2003
Abstract	Subsets of parasympathetic and enteric neurons require neurturin signaling via glial cell line–derived neurotrophic factor family receptor α2 (GFRα2) for development and target innervation. Why GFRα2-deficient (Gfra2 –/–) mice grow poorly has remained unclear. Here, we analyzed several factors that could contribute to the growth retardation. Neurturin mRNA was localized in the gut circular muscle. GFRα2 protein was expressed in most substance P–containing myenteric neurons, in most intrapancreatic neurons, and in surrounding glial cells. In the Gfra2 –/– mice, density of substance P–containing myenteric ganglion cells and nerve bundles in the myenteric ganglion cell layer was significantly reduced, and transit of test material through small intestine was 25% slower compared to wild-type mice. Importantly, the knockout mice had approximately 80% fewer intrapancreatic neurons, severely impaired cholinergic innervation of the exocrine but not the endocrine pancreas, and increased fecal fat content. Vagally mediated stimulation of pancreatic secretion by 2-deoxy-glucose in vivo was virtually abolished. Retarded growth of the Gfra2 –/– mice was accompanied by reduced fat mass and elevated basal metabolic rate. Moreover, the knockout mice drank more water than wild-type controls, and wet-mash feeding resulted in partial growth rescue. Taken together, the results suggest that the growth retardation in mice lacking GFRα2 is largely due to impaired salivary and pancreatic secretion and intestinal dysmotility.
Related Links	http://dx.doi.org/10.1172/jci200317995
Ending Page	716
Page Count	10
Starting Page	707
File Format	PDF
ISSN	00219738
Journal	Journal of Clinical Investigation
Issue Number	5
Volume Number	112
Language	English
Publisher	American Society for Clinical Investigation
Publisher Date	2003-09-01
Access Restriction	Open
Rights Holder	American Society for Clinical Investigation
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine

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