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 μ-type 2, a gene involved in the defense against oxidative stress. Quantitative reverse transcription–polymerase chain reaction relative to a β-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.