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
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.