Analysis of the Structure and Expression of the Human Dopamine D2A Receptor Gene

Abstract

In order to study the possible involvement of dopamine receptors in the pathophysiology of various neurological and psychiatric disorders, we have isolated the human D2A gene. Like the rat D2A gene, the human gene contains at least eight exons and spans at least 52 kb. Exons 2-8 are clustered within 14 kb of genome. Exon 1 is separated from exon 2 by at least 38 kb. We and others have shown that alternative utilization of exon 6 gives rise to alternative D2A transcripts. Despite the extreme size of intron 1, no alternative transcription between exons 1 and 2 can be detected in basal ganglia and pituitary using polymerase chain reaction analysis. The relative abundance and tissue distribution of the alternative D2A transcripts were examined in 18 human brain regions. The relative expression of the transcripts varied by at least 70-fold across the brain regions surveyed. As expected, high levels of transcripts were detected in caudate, putamen, and pituitary. Moderate levels were detected in regions of catecholamine-containing cell bodies and in the amygdala. In contrast to the rat brain, very low levels of transcripts were detected in cortical regions.