HUMAN METABOTROPIC GLUTAMATE-RECEPTOR-1 - MESSENGER-RNA DISTRIBUTION,CHROMOSOME LOCALIZATION AND FUNCTIONAL EXPRESSION OF 2 SPLICE VARIANTS

We have isolated clones from a human brain cDNA library coding for two splice variants of mGluR1. The combined sequences account for 6864 ba se pairs (bp) of the similar to 7 kilobase (kb) transcript seen on nor thern blots of human brain mRNA. The distribution of mGluR1 mRNA in hu man brain is similar to that found in rat brain and the gene for mGluR 1 is localized on human chromosome 6. The mRNA for mGluRl alpha contai ns an open reading frame that codes for a 1194 amino acid protein, whi ch is slightly smaller than rat mGluR1 alpha. The major structural dif ference noted between the human and rat mGluR1 is a deletion of 21 nuc leotides which would result in the loss of seven amino acids in the mi ddle of a proline- and glutamine-rich region of the C-terminal tail of mGluR1 alpha. The 85 bp exon that results in the HmGluR1 beta splice variant was found to code for a protein with two amino acid difference s compared to the rat receptor. Functional and pharmacological charact erization of heterologously expressed human mGluR1 was performed using electrophysiological recordings from Xenopus oocytes and calcium imag ing in HEK-293 cells. No major differences were found in the response of human mGluR1 to typical agonists and antagonists compared to the ra t, or in the behavior of the two splice variants. (C) 1997 Elsevier Sc ience Ltd.