International Mammalian Genome Society

E25 Quantitative Trait Loci Analysis of Salt-Induced Blood Pressure Elevation in C57BL/6J and A/J Mice; Concordance of QTL with Rat and Human Hypertension QTL

Beverly Paigen, Fumihiro Sugiyama, Gary A. Churchill, David Higgins, Conrado Johns, and Haralambos Gavras. The Jackson Laboratory, Bar Harbor, Maine and Boston University School of Medicine, Boston, MA

To investigate the genetic control of salt-induced hypertension, we performed quantitative trait loci (QTL) analysis on 250 mice from an (A/J x C57BL/6J)F1 x C57BL/6J backcross.- Blood pressure in male mice provided with1% salt in drinking water for 2 weeks was measured by tail cuff using the Visitech Systems blood pressure analysis system. Mean blood pressure, based on 10 measurements/day for 5 days after mice were trained to the machine, was 104.8 ± 7.4 in B6, 85.0 ± 5.9 in A, and 101.1 in F1 mice. To find blood pressure QTL, we conducted genome-wide scans using marker-based regression. Permutation testing was used to determine which likelihood ratio statistics were significant. To find gene interactions, we evaluated all possible pairs of markers with two-way ANOVA. Eight significant QTL were found: five, atD1Mit7, D1Mit14, D4Mit288, D5Mit193, andD5Mit409, were based on main effects and three, atD6Mit15, D11Mit82 andD15Mit22., were based on gene interactions. Most of these QTL lie in regions with strong candidate genes for hypertension. Comparison of these QTL with the QTL found for rat and human hypertension show that 7 of the 8 murine QTL are concordant with the rat and at least 5 of the 8 murine QTL are condordant with human QTL. This concordance among species suggests that variation in only a limited number of genes in the pathways affecting blood pressure are likely to have an impact on the final phenotype. In addition, the high degree of concordance suggests that QTL mapping in model organisms can be used to guide the search for human blood pressure QTL.