
pmid: 12624007
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.
Radiation Hybrid Mapping, Genome, Gene Expression Profiling, Quantitative Trait Loci, Chromosome Mapping, Blood Pressure, Chromosomes, Mammalian, Rats, Inbred WKY, Synteny, Rats, Mice, Phenotype, Animals, Congenic, Rats, Inbred SHR, Hypertension, Animals, Humans, Glutathione Transferase, Oligonucleotide Array Sequence Analysis
Radiation Hybrid Mapping, Genome, Gene Expression Profiling, Quantitative Trait Loci, Chromosome Mapping, Blood Pressure, Chromosomes, Mammalian, Rats, Inbred WKY, Synteny, Rats, Mice, Phenotype, Animals, Congenic, Rats, Inbred SHR, Hypertension, Animals, Humans, Glutathione Transferase, Oligonucleotide Array Sequence Analysis
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