Linkage of 11 beta-hydroxylase mutations with altered steroid biosynthesis and blood pressure in the Dahl rat.
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.
Cicila
G T
GT
Department of Macromolecular Biochemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543.
Rapp
J P
JP
Wang
J M
JM
St Lezin
E
E
Ng
S C
SC
Kurtz
T W
TW
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D002417:Cattle; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics*; D013599:Systole
D012982:Sodium, Dietary; D013252:Steroid 11-beta-Hydroxylase