CLONING AND FUNCTIONAL-ANALYSIS OF A POLYMORPHIC VARIANT OF THE OVINEMEL 1A MELATONIN RECEPTOR

We have isolated a novel variant of the Mel la melatonin receptor from an ovine PT cDNA library. Relative to the reported sequence for the M el la melatonin receptor there are 8 changes in the DNA sequence. Only 3 of these result in amino acid substitutions, one in extracellular l oop 3 and two in the carboxy-terminal tail. We have designated the nov el variant of the sheep Mel la receptor Mel 1a(beta), and correspondin gly the previously reported variant Mel la(alpha). As minor changes in the primary amino acid sequence of G-protein-coupled receptors can in fluence their functional characteristics we have accordingly character ized this novel variant of the Mel 1a melatonin receptor. This melaton in receptor displays high affinity binding and inhibits the cAMP secon d messenger pathway in transfected L-celIs demonstrating that this rec eptor is fully functional. PCR analysis shows Mel 1a(beta) is present in several breeds of sheep and suggests that the Mel 1a(beta) receptor was established early in the evolution of the sheep species. (C) 1997 Elsevier Science B.V.