Structural Differences in the Renin Gene of Dahl Salt-Sensitive and Salt-Resistant Rats

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Abstract
Genomic libraries in .lambda. EMBL4 phage were constructed from both inbred Dahl salt-hypertensionsensitive (S) and inbred Dahl salt-hypertension-resistant (R) rats. Overlapping clones containing the renin genes were isolated from these libraries by screening with a renin cDNA probe. Clones were characterized by a combination of restriction mapping and Southern blot analysis. The results showed that the S-rat renin gene is remarkedly different from the R-rat renin gene. The major differences are 1) a 1.2-kilobase (kb) insertion in the first intron of the S-gene which accounts for most of the restriction fragment length polymorphisms found in the renin genes between S and R strains, such as those generated with BgIII [2.7 kb (S)/1.5 kb (R)], EcoRI [6.4 kb (S)/5.2 kb (R)], and HindIII [9.6 kb (S)/8.4 kb (R)]; 2) an additional HindIII site located at the 3'' end of the R-gene which accounts for another HindIII restriction fragment length polymorphisms [25 kb (S)/22 kb, 3.4 kb (R)]; 3) two Smal sites at the 5'' flanking region of the first exon of the S-gene, whereas there is only one Smal site in the corresponding region of the R-gene; and 4) three Aval sites in the first intron of the S-gene in contrast to two Aval sites in the same region of the R-gene. These differences in the renin genes of Dahl rats might effect renin gene expression, which could account for the known strain differences in plasma and tissue renin activities. These structural studies provide a basis for genetic investigation into the relationship of the renin gene to blood pressure in Dahl rats.