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 elements 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 translational initiation codon to -5.6 kb in the 5′ flanking region of the murine receptor gene were found to be sufficient to target gene expression to the brain in transgenic animals. In transient transfection experiments a basal promoter was identified which was functional in both neuronal and nonneuronal cells. Upstream of the basal promoter two repressor domains were found within the 5′ flanking sequence of the receptor gene. These sequences repressed gene activity in all cells except cells of neuronal origin, thus the repressor domains are the primary determinants to generate neuronal cell-specific transcription of the 5-HT₂ receptor gene.