Microarray analysis of rat chromosome 2 congenic strains.
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 mu-type 2, a gene involved in the defense against oxidative stress. Quantitative reverse transcription-polymerase chain reaction relative to a beta-actin standard confirmed the microarray results with SHRSP mRNA at 8.56 x 10(-4) +/-1.6 x 10(-4) compared with SP.WKYGla2c* 3.67 x 10(-3)+/-2.8 x 10(-4) (95% CI -3.9 x 10(-3) to -1.8 x 10(-3); P=0.0034) and WKY 4.03 x 10(-3)+/-5.1 x 10(-4); (95% CI -5.4 x 10(-3) to -8.9 x 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.
Pubmed ID: 12624007 RIS Download
Animals | Animals, Congenic | Blood Pressure | Chromosome Mapping | Chromosomes, Mammalian | Gene Expression Profiling | Genome | Glutathione Transferase | Humans | Hypertension | Mice | Oligonucleotide Array Sequence Analysis | Phenotype | Quantitative Trait Loci | Radiation Hybrid Mapping | Rats | Rats, Inbred SHR | Rats, Inbred WKY | Synteny