Metabotropic glutamate receptor subtype 6 (
mGluR6) is restrictedly expressed in the
retinal ON bipolar cells and ablation of mouse
mGluR6 by gene targeting results in a loss of ON responses to light stimulus and impairs the detection of visual contrasts. We have isolated genomic clones containing the human
mGluR6 gene and determined the whole nucleotide sequence of the
mGluR6 gene. The transcription initiation site of the human
mGluR6 gene has been identified using primer extension analysis in combination with
reverse transcriptase-mediated polymerase chain reaction analysis of human
retinal RNA, while the termination of the
mGluR6 mRNA has been assigned by the analysis of rapid amplification of 3'-cDNA ends. The human
mGluR6 gene consists of 16,742 base pairs with 10 exons separated by nine introns. The human
mGluR6 is composed of 877
amino acid residues with a
signal peptide of 24
amino acid residues and the mature
protein shows a 94.6% homology with the rat counterpart. A CpG-rich island is present at exon 1 and its preceding putative promoter region and this unusual sequence, like several tissue-specific genes, may be important for a specific expression of the
mGluR6 gene in the retinal bipolar cells. The human
mGluR6 gene has been mapped to chromosome 5q35 by the analyses of blot hybridization of
a DNA panel of human/mouse/hamster somatic cell hybrids and fluorescence in situ hybridization of human chromosomes. This study should provide the genetic basis for not only better understanding the molecular mechanism underlying a tissue-specific expression of the
mGluR6 gene but also exploring a potential defect in human
mGluR6 in a certain inherited
eye disease.