Background gene expression in rat kidney: influence of strain, gender, and diet

In order to gain better insight into factors (strain, gender, and diet) influencing background variability in kidney gene expression, we examined the transcriptomes of male and female Crl: CD(SD)IGSBR (Sprague-Dawley [SD]) and CDF(Fischer 344)/ CrlBR rats maintained for 19 days on three different diets (ad libitum [AL], diet restriction-75% of AL, and casein-based phytoestrogen-free diet). Kidney RNA was analyzed using Agilent Rat oligo microarrays (approximately 20,000 genes). Principal component analysis demonstrated that strain and gender have the most impact on the variability in gene expression, while diet had a lesser effect. The majority of the affected genes differed by a magnitude of four-fold or less between strains/gender, with some previously known to be sex-hormone regulated (SLC22A7 and SLC21A1). One gene of particular interest was ornithine decarboxylase, a significant marker of cell proliferation and tumor promotion, which was expressed at an 18-fold greater level in SD rats. Further analysis revealed that the difference in expression was due to the use of an alternate polyadenylation signal resulting in the production of two different sizes of transcripts. These results demonstrate that gender and strain have significant influence on gene expression which could be a confounder when comparing results, especially when it involves predictive fingerprint/patterns.