THE 5' FLANKING REGION OF THE RAT BETA-3-ADRENERGIC RECEPTOR GENE - DIVERGENCE WITH THE HUMAN GENE AND IMPLICATIONS FOR SPECIES-SPECIFIC GENE-EXPRESSION

beta(3)-adrenergic receptor mRNAs exhibit species-specific expression (human vs. rodent) in distinct anatomical regions and appear to be exp ressed abundantly within rodent adipose tissue, but only at low levels within corresponding human tissues. In order to determine the genetic basis of the differential expression of the rat and human beta(3)-adr energic receptor genes, we cloned and sequenced the rat gene and compa red the 5' flanking regions of the two genes to identify potential dis criminators in transcriptional regulation. We have round that the rat and human beta(3)-adrenergic receptor 5' flanking regions are only 67% similar, unlike the close sequence similarity observed between the co ding blocks (>90%) and also observed between species for the 5' flanki ng regions of other beta-adrenergic receptor subtype genes (>90%). In addition, the rat beta(3)-adrenergic receptor gene lacks the four pote ntial cAMP responsive elements identified within the 5' flanking regio n of the human receptor gene. The striking divergence in regulatory se quences between the rat and human beta(3)-adrenergic receptor genes ma y potentially explain the differences in species-specific expression a nd tissue localization of the rat and human receptor mRNAs.