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

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Abstract

11 β-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% NaC1 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.

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Authors and Affiliations

  1. Department of Physiology and Molecular Medicine, Medical College of Ohio, 3000 Arlington Avenue, P.O. Box 10008, 43699-0008, Toledo, Ohio, USA

    George T. Cicila, Oksana I. Dukhanina, Michael R. Garrett, Howard Dene & John P. Rapp

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

    Theodore W. Kurtz

  3. Department of Internal Medicine, University of Iowa, 52242, Iowa City, Iowa, USA

    Roxanne Walder

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  1. George T. Cicila
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  2. Oksana I. Dukhanina
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  3. Theodore W. Kurtz
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  4. Roxanne Walder
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  5. Michael R. Garrett
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  6. Howard Dene
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  7. John P. Rapp
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Cicila, G.T., Dukhanina, O.I., Kurtz, T.W. et al. Blood pressure and survival of a Chromosome 7 congenic strain bred from Dahl rats. Mammalian Genome 8, 896–902 (1997). https://doi.org/10.1007/s003359900607

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  • DOI: https://doi.org/10.1007/s003359900607

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