THE 5' FLANKING REGION OF THE SEROTONIN-2 RECEPTOR GENE DIRECTS BRAIN-SPECIFIC EXPRESSION IN TRANSGENIC ANIMALS

The neuron is the predominant cell type expressing the serotonin 2 (5- HT2) receptor in the central nervous system. Transcriptional control e lements involved in the restriction of 5-HT2 receptor gene expression to neuronal cells and tissues were studied using both transgenic mice and cultured cells. Sequences extending from a site near the translati onal initiation codon to -5.6 kb in the 5' flanking region of the muri ne receptor gene were found to be sufficient to target gene expression to the brain in transgenic animals. In transient transfection experim ents a basal promoter was identified which was functional in both neur onal and nonneuronal cells. Upstream of the basal promoter two repress or domains were found within the 5' flanking sequence of the receptor gene. These sequences repressed gene activity in all cells except cell s of neuronal origin, thus the repressor domains are the primary deter minants to generate neuronal cell-specific transcription of the 5-HT2 receptor gene.