Cicila G T, Rapp J P, Wang J M, St Lezin E, Ng S C, Kurtz T W
Department of Macromolecular Biochemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543.
Nat Genet. 1993 Apr;3(4):346-53. doi: 10.1038/ng0493-346.
In Dahl salt-hypertension sensitive (S) and resistant (R) strains fed a high NaCl diet, 11 beta-hydroxylase polymorphisms cosegregate with the adrenal capacity to synthesize 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) and blood pressure. The R rat carries an 11 beta-hydroxylase allele that: (i) differs from those of 12 other rat strains; (ii) is associated with a uniquely reduced capacity to synthesize 18-OH-DOC; and (iii) encodes 5 amino acid substitutions in the 11 beta-hydroxylase protein. The robust salt-resistance of the Dahl R rat may be due in part to reduced synthesis of the mineralocorticoid 18-OH-DOC stemming from mutations in the 11 beta-hydroxylase gene. 11 beta-hydroxylase, located on rat chromosome 7, is the first candidate gene identified in an animal model in which coding sequence mutations have been linked to the regulation of blood pressure.
