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Identification of Rtel1, Edn3, and Dnajc5 as candidate genes for rat chromosome 3 blood pressure Quantitative Trait Loci (QTLs) by gene expression profiling under multiple salt‐loading conditions

Previous work, comparing congenic rat strains carrying Dahl salt‐resistant (R) rat chromosome 3 (RNO3) alleles on a Dahl salt‐sensitive (S) rat background with the hypertensive S rats defined two blood pressure (BP) QTL‐containing intervals. Renal gene expression profiling of S.R(ET3×1) and S.R(ET3×2) congenic substrain rats, compared to S rats, was conducted in two microarray experiments using Affymetrix Rat RAE230 GeneChip sets. The first examined renal expression after 1) maintenance on a low dietary (0.4% NaCl) salt intake or 2) following acute (24 hour) exposure to an elevated dietary salt (4% NaCl) intake, identifying differentially expressed genes by two‐way analysis of variance. The second examined renal expression following chronic (28 day) exposure to an elevated dietary salt (2% NaCl) intake, identifying differential expression by Significance Analysis of Microarrays thresholding. Ingenuity Pathways Analysis (IPA) was used to highlight cellular molecular networks containing differentially expressed probesets likely altered among the three strains. Candidate genes were defined as mapping to RNO3 congenic regions and being 1) differentially‐expressed and/or 2) interacting with one or more genes in an IPA‐identified molecular network. Differential expression of Rtel1, Edn3, and Dnajc5 was found in both the acute and chronic NaCl‐loading experiments by qRT‐PCR.