Regional expression and regulation of alternative forms of mRNAs derived from two distinct transcription initiation sites of the rat mGluR5 gene.

Metabotropic glutamate receptor (mGluR) subtype 5 is expressed in both neuronal and glial cells and is thought to play an important role in neuronal plasticity. This expression is up-regulated during the early postnatal period and is induced in cultured astrocytes by specific growth factors. To investigate the mechanism underlying the regulation of mGluR5 expression, we isolated and characterized genomic clones containing the 5'-upstream exons and their flanking regions of the mGluR5 gene. On the basis of the mGluR5 genomic structure, cDNA recloning of the 5'-extreme region of mGluR5 as well as primer extension analysis indicated that mGluR5 mRNA is generated from two alternative first exons, termed exon 1A and exon 1B, which are separated by 1,949 bp and then connected to the common exon 2. Northern blot and in situ hybridization analyses indicated that two distinct transcription initiation sites are commonly used in the expression of mGluR5 mRNA in various, but specialized, brain regions and that these two alternative forms of mGluR5 mRNA are similarly up-regulated or down-regulated during the early postnatal period, depending on the brain regions. The two mRNAs are also expressed in cultured astrocytes but respond differently to growth factor-mediated induction. This study provides the genetic basis indicating the diverse mechanisms involved in the regulation of mGluR5 expression.