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.
McBride
Martin W
MW
BHF Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow, G11 6NT, Scotland.
Carr
Fiona J
FJ
Graham
Delyth
D
Anderson
Niall H
NH
Clark
James S
JS
Lee
Wai K
WK
Charchar
Fadi J
FJ
Brosnan
M Julia
MJ
Dominiczak
Anna F
AF
D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D020869:Gene Expression Profiling; D016678:Genome; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D040641:Quantitative Trait Loci; D021101:Radiation Hybrid Mapping; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D026801:Synteny
D005982:Glutathione Transferase