Blood pressure and survival of a Chromosome 7 congenic strain bred from Dahl rats

Abstract

11 beta-hydroxylase (Cyp11b1) mutations were previously linked to altered steroid biosynthesis and blood pressure in Dahl salt-resistant (R) and Dahl salt-sensitive (S) rats. In the present work, interval mapping identified a putative blood pressure quantitative trait locus (QTL) near Cyp11b1 in an F1(SxR)xS population (LOD = 2.0). Congenic rats (Designated S.R-Cyp11b) were constructed by introgressing the R-rat Cyp11b1 allele into the S strain. S.R-Cyp11b rats had significantly lower blood pressure and heart weight compared with S rats, proving the existence of a blood pressure QTL on Chromosome (Chr) 7 despite the fact that QTL linkage analysis of blood pressure never achieved stringent statistical criteria for significance. To test the effects of the introgressed region on blood pressure and survival, S.R.-Cyp11b and S rats were maintained on a 4% NaCl diet until they died or became moribund. Analysis of variance (ANOVA) indicated significant strain differences in blood pressure and days survived (P < 0.0001 for both) as well as gender differences in days survived (P = 0.0003). Kaplan-Meier survival analysis also found significant strain (P < 0.0001) and gender (P = 0.007) differences in days survived. However, when the effects of blood pressure were removed, significant strain differences in survival essentially disappeared. This suggests that the increased survival of S.R-Cyp11b rats was largely due to their decreased blood pressure and thus strongly corroborates the existence of a blood pressure QTL on Chr 7 near or at Cyp11b1.

Substitution Mapping in Dahl Rats Identifies Two Distinct Blood Pressure Quantitative Trait Loci Within 1.12- and 1.25-Mb Intervals on Chromosome 3

“…Two backcross F 1 (S 3 R) 3 S populations (n ¼ 150 rats) were used to construct a detailed linkage map of RNO3. The breeding and phenotyping of these populations were previously described in detail (Cicila et al 1997(Cicila et al , 1999.…”

“…PCR amplification and gel electrophoresis were performed as previously described (Cicila et al 1997). Additional microsatellite markers were placed on the RNO3 linkage map to further define the extent of R-rat chromosome introgressed into the congenic strain and substrains.…”

Successful Isolation of a Rat Chromosome 1 Blood Pressure Quantitative Trait Locus in Reciprocal Congenic Strains

“…Previous attempts [34][35][36][37][38][39][40][41][42] at isolating blood pressure QTLs in congenic strains have mostly, apart from a few exceptions, 34 -35 involved transferring the region in a single direction. In the majority of cases, this has been from the normotensive strain into the hypertensive strain, on the assumption that demonstrating a decrease in blood pressure would be easier than an increase.…”

Congenic Rats For Hypertension: How Useful Are They For The Hunting Of Hypertension Genes?

“…the interval within odds of 100 : 1 of the maximum log of odds (LOD) score); or (ii) to introgress a particular candidate locus. For DS, all congenics, except for the renin locus on chromosome 13 4,5 and the Cyp11b locus on chromosome 7, 6 were made to cover the entire QTL region. As a result, they have large chromosomal fragments (35-84 cM) transferred from the donor strains.…”