STRUCTURE AND ALTERNATIVE PROMOTERS OF THE MOUSE GLUTAMIC-ACID DECARBOXYLASE-67 GENE

gamma-Aminobutyric acid is synthesized by glutamic acid decarboxylase (GAD), which has two forms, GAD65 and GAD67. Genomic clones coding mou se GAD67 (mGAD67) have been isolated. The restriction map of the overl apping clones covers a region of more than 45 kb of genomic DNA. The m GAD67 gene contains 16 translated exons in addition to an exon which i s preferentially expressed in foetal brain. The rapid amplification of 5'-cDNA ends showed that mGAD67 gene transcripts have two different 5 '-untranslated regions. Analysis of the genomic clones encompassing th e 5'-exons revealed that the two transcripts arose from a single gene by alternative splicing using two different donor sites and a common a cceptor. The exons were found 1.5 and 0.6 kb upstream of exon 1. The c orresponding promoter regions of these exons have a number of putative regulatory elements, including Sp1-and Krox-24-binding sites. Analysi s of mGAD67 transcripts demonstrated that each of the 5'-untranslated exons was expressed in mouse brain. In contrast, exon 0B, but not exon OB; was expressed in mouse testis and pancreas. These results suggest that these transcripts may be regulated under the control of independ ent promoters.