GENE STRUCTURE AND 5'-FLANKING REGULATORY REGION OF THE MURINE SEROTONIN TRANSPORTER

By modulating the magnitude and duration of postsynaptic responses, ca rrier-facilitated serotonin (5-HT) transport into and release from the presynaptic neuron is central to the fine tuning of serotonergic neur otransmission. The 5-HT transporter (5-HTT) is the prime target for wi dely used antidepressants, psychostimulants, drugs of abuse and neurot oxins. We have isolated the gene encoding the murine 5-HTT and determi ned the sequence of all exons including adjacent intronic regions and similar to 3.6 kb of the 5'-flanking regulatory region. The murine 5-H TT gene is composed of 14 exons spanning similar to 34 kb. The single gene transcript after splicing is 2744 bp in length and it contains 18 6 bp of 5' untranslated region (5'-UTR) and 668 bp of 3'-UTR. A TATA-l ike motif and several potential binding sites for transcription factor s including API, AP2, AP4, SPL as well as CRE- and GRE-like motifs are present in the GC-rich 5'-flanking region. The characterization of mu rine 5-HTT cDNA and genomic organization will facilitate studies of 5- HT uptake function with molecular pharmacologic and transgenic strateg ies as well as investigations of its role in quantitative traits and p sychiatric disorders.