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Microarray analysis of rat chromosome 2 congenic strains
Martin W McBride1, Fiona J Carr, Delyth Graham
1BHF Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow, G11 6NT, Scotland.
Hypertension (Dallas, Tex. : 1979)
|March 8, 2003
Summary
A congenic rat strain (SP.WKYGla2c*) significantly reduced blood pressure compared to its hypertensive parent (SHRSP). This strain showed decreased expression of glutathione S-transferase mu-type 2, a gene linked to oxidative stress defense.
Area of Science:
- Genetics and Genomics
- Cardiovascular Research
- Molecular Biology
Background:
- Essential hypertension is a complex polygenic trait in humans with unknown genetic underpinnings.
- The stroke-prone spontaneously hypertensive rat (SHRSP) serves as a valuable animal model for studying human hypertension.
- Quantitative trait loci (QTLs) associated with blood pressure regulation have been mapped to rat chromosome 2 in SHRSP models.
Purpose of the Study:
- To investigate the genetic basis of hypertension using a congenic rat strain.
- To identify genes and pathways involved in blood pressure regulation.
- To characterize the effects of introgressing a specific chromosomal region from a normotensive strain into a hypertensive background.
Main Methods:
- Development of the SP.WKYGla2c* congenic strain by introgressing rat chromosome 2 from Wistar Kyoto (WKY) rats into the SHRSP genetic background.
- Measurement of systolic and diastolic blood pressures in parental and congenic strains.
- Genome-wide microarray expression profiling to identify differentially expressed genes.
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to validate gene expression changes.
Main Results:
- The SP.WKYGla2c* congenic strain exhibited significantly reduced systolic and diastolic blood pressures compared to the SHRSP parental strain.
- Microarray analysis revealed a significant reduction in the expression of glutathione S-transferase mu-type 2 (Gstm2) in the congenic strain.
- qRT-PCR confirmed the decreased expression of Gstm2 in the SP.WKYGla2c* strain relative to both SHRSP and WKY strains.
- Regions of conserved synteny containing the Gstm2 gene were identified on mouse chromosome 3 and human chromosome 1.
Conclusions:
- Introgression of a specific region of rat chromosome 2 into the SHRSP background effectively reduces blood pressure.
- Downregulation of glutathione S-transferase mu-type 2 (Gstm2) is associated with reduced blood pressure in this congenic model.
- Gstm2, involved in oxidative stress defense, may play a role in hypertension regulation.
- The identified conserved synteny highlights potential homologous genes in other species relevant to hypertension research.