Microarray Analysis of Rat Chromosome 2 Congenic Strains

Abstract—Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. The stroke-prone spontaneously hypertensive rat (SHRSP) is a model of human essential hypertension, and a number of reproducible blood pressure regulation quantitative trait loci have been found to map to rat chromosome 2. The SP.WKYGla2c* congenic strain was produced by introgressing a region of rat chromosome 2 from the normotensive Wistar Kyoto (WKY) strain into the genetic background of the SHRSP. Systolic and diastolic blood pressures were significantly reduced in the SP.WKYGla2c* compared with the SHRSP parental strain (198/134±6.1/3.3 versus 172/120±3.8/3.4 mm Hg; F=15.8/8.1, P =0.0009/0.013). Genome-wide microarray expression profiling was undertaken to identify differentially expressed genes among the parental SHRSP, WKY, and congenic strain. We identified a significant reduction in expression of glutathione S-transferase &mgr;-type 2, a gene involved in the defense against oxidative stress. Quantitative reverse transcription–polymerase chain reaction relative to a &bgr;-actin standard confirmed the microarray results with SHRSP mRNA at 8.56×10−4 ±1.6×10−4 compared with SP.WKYGla2c* 3.67×10−3±2.8×10−4 (95% CI −3.9×10−3 to −1.8×10−3;P =0.0034) and WKY 4.03×10−3±5.1×10−4; (95% CI −5.4×10−3 to −8.9×10−4;P =0.027). We also identified regions of conserved synteny, each containing the Gstm2 gene, on mouse chromosome 3 and human chromosome 1.