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Linkage of 11β-hydroxylase mutations with altered steroid biosynthesis and blood pressure in the Dahl rat

Nature Genetics volume 3, pages 346–353 (1993)Cite this article

Abstract

In Dahl salt-hypertension sensitive (S) and resistant (R) strains fed a high NaCI diet, 11β-hydroxylase polymorphisms cosegregate with the adrenal capacity to synthesize 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) and blood pressure. The R rat carries an 11β-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 11β-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 11β-hydroxylase gene. 11β-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.

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Author notes

  1. George T. Cicila

    Present address: Department of Medicine, University of Missouri, Columbia, Missouri, 65212, USA

Authors and Affiliations

  1. Department of Macromolecular Biochemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, 08543

    George T. Cicila & Shi Chung Ng

  2. Department of Biology, Princeton University, Princeton, New Jersey, 08544, USA

    George T. Cicila & Shi Chung Ng

  3. Department of Medicine, Medical College of Ohio, Toledo, Ohio, 43699, USA

    John P. Rapp

  4. Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California, 94143, USA

    Jia-Ming Wang, Elizabeth St. Lezin & Theodore W. Kurtz

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Cicila, G., Rapp, J., Wang, JM. et al. Linkage of 11β-hydroxylase mutations with altered steroid biosynthesis and blood pressure in the Dahl rat. Nat Genet 3, 346–353 (1993). https://doi.org/10.1038/ng0493-346

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