INTRONIC SEQUENCES ARE INVOLVED IN NEURAL TARGETING OF HUMAN DOPAMINETRANSPORTER GENE-EXPRESSION

Dopamine transporter (DAT) plays a key role in terminating synaptic do paminergic transmission. DAT acts exclusively on the plasma membrane o f presynaptic dopaminergic neurons and DAT gene is an appropriate mode l for the study of dopaminergic neuron-specific regulation of gene act ivity. DAT represents an important target for widely used neuroleptic drugs and psychostimulants and for catecholamine-selective neurotoxins . Functional abnormalities of DAT have been implicated in diverse neur ologic and psychiatric disorders. Understanding the mechanisms regulat ing human DAT gene activity is an important step towards elucidation o f the molecular bases of a number of disorders and psychostimulant dru g abuse and dependence. In this study we have cloned and characterised a 7-kb segment of the human DAT gene which includes at least 4 kb of its 5'-flanking region, localised its essential, or core-promoter, and identified the region involved in regulation of DAT neurospecific exp ression. (C) 1997 Academic Press.