High-resolution mapping of the blood pressure QTL on chromosome 7 using Dahl rat congenic strains.
It was previously shown using Dahl salt-sensitive (S) and salt-resistant (R) rats that a blood pressure quantitative trait locus (QTL) was present on rat chromosome 7. In the present work, this QTL was localized to a region less than 0.54 cM in size on the linkage map using a series of congenic strains. This region was contained in a single yeast artificial chromosome that was 220 kb long. This small segment still contained the primary candidate locus Cyp11b1 (11beta-hydroxylase), but the adjacent candidate genes Cyp11b2 (aldosterone synthase) and Cyp11b3 were ruled out. It is concluded that 11beta-hydroxylase, through its known genetic variants altering the production of 18-hydroxy-11-deoxy corticosterone, is very likely to account for the blood pressure QTL on chromosome 7 in the Dahl rat model of hypertension. This QTL accounts for about 23 mm Hg under the condition of 2% NaCl diet for 24 days.
Cicila
G T
GT
Department of Physiology and Molecular Medicine, Medical College of Ohio, Toledo, Ohio 43614, USA.
Garrett
M R
MR
Lee
S J
SJ
Liu
J
J
Dene
H
H
Rapp
J P
JP
D000483:Alleles; D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure / Q000235:genetics*; D018244:Chromosomes, Artificial, Yeast; D003001:Cloning, Molecular; D003434:Crossing Over, Genetic; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000096:biosynthesis; D005260:Female; D006321:Heart; D006973:Hypertension / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D009929:Organ Size; D020161:Physical Chromosome Mapping; D019655:Quantitative Trait, Heritable; D051381:Rats; D020303:Rats, Inbred Dahl; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000494:pharmacology; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics*
D012982:Sodium, Dietary; C042509:18-hydroxydeoxycorticosterone; D003900:Desoxycorticosterone; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase