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Cloning, mRNA Distribution and Chromosomal Localisation of the Gene for Glial Cell Line-Derived Neurotrophic Factor Receptor β, a Homologue to GDNFR-α

DDBJ/EMBL/GenBank accession nos AF003825 and U93703 Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for central dopaminergic neurons, motor neurons and several other populations of neurons in the central and peripheral nervous system. GDNF and its receptor complex of c-RET tyrosine kinase and a glycosyl-phosphatidylinositol linked protein GDNFR-α are of great interest due to their potential use in the therapy of Parkinson’s and motoneuron diseases. We have cloned the human and rat cDNA sequences of GDNFR-β, a new gene encoding for a 464 amino acid long homologue of GDNFR-α, and assign the locus of this new gene to human chromosome 8p21‐22 and mouse chromosome 14D3-E1. Similarly to GDNFR-α, GDNFR-β mediates GDNF-induced Ret autophosphorylation in transfected cells. By northern hybridisation we show that the transcript level of human GDNFR-β mRNA is high in the adult brain, intestine and placenta and in fetal brain, lung and kidney. Studied by in situ hybridisation, GDNFR-β mRNA shows in E17 rat embryo different distribution to that of GDNFR-α mRNA, especially, in adrenal gland, kidney and gut. In the developing nervous system, GDNFR-β mRNA expression is restricted to certain neuronal populations, while GDNFR-α mRNA is widely expressed also in nonneuronal cells. The distinct tissue distribution of GDNFR-β mRNA and its ability to mediate GDNF signal in transfected cells suggest a role in signal transduction of GDNF and, possibly, related neurotrophic factors in vivo.