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ToxSci Advance Access published online on August 17, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl082
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received June 13, 2006
Accepted August 15, 2006

Systems Toxicology

Background Gene Expression in Rat Kidney: Influence of Strain, Gender, and Diet

Shawn D. Seidel 1, Shao-Ching Hung 2, H. Lynn Kan 1, and B. Bhaskar Gollapudi 1 *

1 Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674
2 Analytical Sciences, The Dow Chemical Company, Midland, MI, 48674

* To whom correspondence should be addressed.
B. Bhaskar Gollapudi, E-mail: bhaskargollap{at}dow.com


  Abstract

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 3 different diets (ad libitum, diet restriction - 75% of ad libitum, 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 effected genes differed by a magnitude of 4-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 (ODC), a significant marker of cell proliferation and tumor promotion, which was expressed at an 18-fold greater level in SD. 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.

Keywords: kidney; microarray; ornithine decarboxylase; gender; strain; diet.
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