The 5' flanking region of the rat β₃-adrenergic receptor gene: Divergence with the human gene and implications for species-specific gene expression

β₃-adrenergic receptor mRNAs exhibit species-specific expression (human vs. rodent) in distinct anatomical regions and appear to be expressed 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 β₃-adrenergic receptor genes, we cloned and sequenced the rat gene and compared the 5' flanking regions of the two genes to identify potential discriminators in transcriptional regulation. We have found that the rat and human β₃-adrenergic receptor 5' flanking regions are only 67% similar, unlike the close sequence similarity observed between the coding blocks (> 90%) and also observed between species for the 5' flanking regions of other βadrenergic receptor subtype genes (> 90%). In addition, the rat β₃-adrenergic receptor gene lacks the four potential cAMP responsive elements identified within the 5' flanking region of the human receptor gene. The striking divergence in regulatory sequences between the rat and human β₃-adrenergic receptor genes may potentially explain the differences in species-specific expression and tissue localization of the rat and human receptor mRNAs.