Endocrine Abstracts (2002) 3 OC5

Identification of differentially expressed genes in rat chromosome 2 congenic strains

MW McBride, FJ Carr, D Graham, JS Clark, P Strahorn, NH Anderson & AF Dominiczak

Medicine and Therapeutics, University of Glasgow, Glasgow, UK.

Objective: To construct rat congenic strains to confirm and narrow down a region on rat chromosome 2 previously implicated in blood pressure regulation. To determine expression profiles and identify differentially expressed genes between congenic strain and respective parental strain using microarray technology.

Design and Methods: Total RNA was prepared from whole kidney homogenates from 2x parental SHRSPGla and 2x SP.WKYGla2a congenic rats. Expression profiles were determined using the Rat U34 genome set GeneCHIP (Affymetrix). Differentially expressed genes were identified by multiple pairwise comparison using the data mining tool version 2.0 (Affymetrix).

Results: Expression profiling experiments, with a fold change greater than 2, identified 179 differentially expressed genes. 118 genes were up regulated in the SP.WKYGla2a congenic strain and 61 down regulated compared to the SHRSPGla parental strain. Using BLAST and Locuslink at least 7 of these differentially expressed genes were mapped in silico and confirmed by radiation hybrid analysis to the transferred chromosomal segment of rat chromosome 2.

Conclusion: We have isolated a region on rat chromosome 2 which may harbour gene(s) responsible for blood pressure regulation. We have identified at least 7 differentially expressed genes that map to the implicated region. These differentially expressed genes may be responsible for hypertension in this model and may be interrogated further through comparative genome analysis in human studies.

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