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Physiol. Genomics 31: 228-235, 2007. First published June 12, 2007; doi:10.1152/physiolgenomics.00280.2006
1094-8341/07 $8.00
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Received 18 December 2006; accepted in final form 11 June 2007.
Physiological Genomics 31:228-235 (2007)
1094-8341/07 $8.00 © 2007 American Physiological Society

Multiple blood pressure loci on rat chromosome 13 attenuate development of hypertension in the Dahl S hypertensive rat

Carol Moreno1,2, Mary L. Kaldunski1, Tao Wang2,3, Richard J. Roman1,4, Andrew S. Greene1,5, Jozef Lazar1,6, Howard J. Jacob1,2,7 and Allen W. Cowley, Jr.1

1 Department of Physiology, Milwaukee, Wisconsin
2 Human and Molecular Genetics Center, Milwaukee, Wisconsin
3 Division of Biostatistics, Milwaukee, Wisconsin
4 Kidney Disease Center, Milwaukee, Wisconsin
5 Biotechnology and Bioengineering Center, Milwaukee, Wisconsin
6 Department of Dermatology, Milwaukee, Wisconsin
7 Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin

Previous studies have indicated that substitution of chromosome 13 of the salt-resistant Brown Norway BN/SsNHsdMcwi (BN) rat into the genomic background of the Dahl salt-sensitive SS/JrHsdMcwi (SS) rat attenuates the development of salt-sensitive hypertension and renal damage. To identify the regions within chromosome 13 that attenuate the development of hypertension during a high-salt diet in the SS rat, we phenotyped a series of overlapping congenic lines covering chromosome 13, generated from an intercross between the consomic SS-13BN rat and the SS rat. Blood pressure was determined in chronically catheterized rats after 2 wk of high-salt diet (8% NaCl) together with microalbuminuria as an index of renal damage. Four discrete regions were identified, ranging in size from 4.5 to 16 Mbp, each of which independently provided significant protection from hypertension during high-salt diet, reducing blood pressure by 20–29 mmHg. Protection was more robust in female than male rats in some of the congenic strains, suggesting a sex interaction with some of the genes determining blood pressure during high-salt diet. Among the 23 congenic strains, several regions overlapped. When three of the "protective" regions were combined onto one broad congenic strain, no summation effect was seen, obtaining the same decrease in blood pressure as with each one independently. We conclude from these studies that there are four regions within chromosome 13 containing genes that interact epistatically and influence arterial pressure.

quantitative trait loci; congenic strain; consomic strain; genetic epistasis; linkage




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