Retarded growth and deficits in the enteric and parasympathetic nervous system in mice lacking GFR alpha 2, a functional neurturin receptor

Citation
J. Rossi et al., Retarded growth and deficits in the enteric and parasympathetic nervous system in mice lacking GFR alpha 2, a functional neurturin receptor, NEURON, 22(2), 1999, pp. 243-252
Citations number
60
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEURON
ISSN journal
08966273 → ACNP
Volume
22
Issue
2
Year of publication
1999
Pages
243 - 252
Database
ISI
SICI code
0896-6273(199902)22:2<243:RGADIT>2.0.ZU;2-E
Abstract
Glial cell line-derived neurotrophic factor (GDNF) and a related protein, n eurturin (NTN), require a GPI-linked coreceptor, either GFR alpha 1 or GFR alpha 2, for signaling via the transmembrane Ret tyrosine kinase. We show t hat mice lacking functional GFR alpha 2 coreceptor (Gfra2(-/-)) are viable and fertile but have dry eyes and grow poorly after weaning, presumably due to malnutrition. While the sympathetic innervation appeared normal, the pa rasympathetic cholinergic innervation was almost absent in the lacrimal and salivary glands and severely reduced in the small bowel. Neurite outgrowth and trophic effects of NTN at low concentrations were lacking in Gfra2(-/- ) trigeminal neurons in vitro, whereas responses to GDNF were similar betwe en the genotypes. Thus, GFRa2 is a physiological NTN receptor, essential fo r the development of specific postganglionic parasympathetic neurons.