MUTATIONS IN THE FIRST INTRON OF THE SHR RENIN GENE DISRUPT PUTATIVE REGULATORY ELEMENTS

1. Four single base mutations unique to the spontaneously hypertensive rat (SHR) were identified in the first 1100 base pairs of its renin g ene first intron when compared to that of Wistar-Kyoto and Sprague-Daw ley normotensive rats. 2. These mutations were found to fall within th e consensus sequences for a number of transcription factors and thus m ay alter the affinity of these putative transcription factor binding s ites. 3. The reported overexpression of the renin gene in the SHR may therefore result from these structural abnormalities and, in turn, res ult in a tissue angiotensin-dependent hypertension in this strain.