International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany

Plenary Presentations * Oral Presentations *
Poster Presentations: Behavioural Genetics and Genomics * Development and Stem Cells * Functional Genome Analysis * Mouse Models of Human Disease * Mouse System Biology Bioinformatics * Multigenic and Multifactorial Trait Analysis * Nutrition and Metabolic Disease * Phenotyping Methods Imaging * The Genetics and Genomics of Infectious Disease *
Verne Chapman Memorial Lecture * Table of Contents * Sponsor/Exhibitor List * Awards * Photographs

---

POSTER 165 - INTERACTING QTL ON CHROMOSOMES 6 AND 15 UNDERLIE SALT-INDUCED HYPERTENSION BY REDUCING SODIUM EXCRETION

DiPetrillo K
The Jackson Laboratory

Co-Authors: Sheehan S, Whitmore H, Taylor E, and Paigen B
Institutions: The Jackson Laboratory

Hypertension represents a significant medical problem in Western societies. Salt-sensitive hypertension confers increased risk of cardiovascular and renal disease, and salt-sensitive changes in blood pressure are associated with increased mortality. We previously identified interacting quantitative trait loci (QTL; C57BL/6J Chr 15 with A/J Chr 6) in mice that contribute to salt-sensitive hypertension. In the present study, we determined that mice containing high blood pressure alleles at both interacting loci (B6.A-Chr 6 consomic) display significantly reduced urinary sodium concentrations compared to C57BL/6J mice (189.9±19 vs. 285.0±7 mM on 1% salt-water). Using a series of reciprocal overlapping congenic strains, we subsequently narrowed the Chr 6 QTL region to 27cM. In addition, data from the overlapping congenic strains suggests the presence of two genes underlying the QTL. Plausible candidate genes within this region include Scnn1a (epithelial sodium channel alpha subunit) and Tnfrsf1a (tumor necrosis factor receptor 1). In conclusion, decreased renal sodium excretion is likely the physiological mechanism mediating the effect of the interacting QTL on Chrs 6 and 15 for salt-induced hypertension. Scnn1a and Tnfrsf1a are plausible candidate genes underlying the QTL on Chr 6. Further research to identify the interacting genes underlying these QTL will enhance our understanding of the pathophysiological basis of salt-sensitive hypertension and possibly provide novel therapeutic targets for treatment of the disease.