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Coordinated changes in xenobiotic metabolizing enzyme (XME) gene expression through the life stages of the male C57BL/6 mouse
Citation:
LEE, J. S., W. O. WARD, J. Liu, H. REN, R. GRINDSTAFF, M. H. GEORGE, D. A. DELKER, AND C. CORTON. Coordinated changes in xenobiotic metabolizing enzyme (XME) gene expression through the life stages of the male C57BL/6 mouse. Presented at American Aging Association's 37th Annual Meeting-The Role of Genes, Environment and Chance in Determining Aging, Boulder, CO, May 30 - June 02, 2008.
Impact/Purpose:
To support MYP Human Health
Description:
Metabolic homeostasis of the organism is maintained by the liver's ability to detoxify and eliminate xenobiotics. This is accomplished, in part, by the expression of XMEs, which metabolize xenobiotics and determine whether exposure will result in toxicity. Some evidence indicates age may alter the ability of organisms to metabolize and excrete xenobiotics, but the degree to which age affects these processes is not known. This project was designed to examine the changes in XMEs from early to late life stages in male C57BL/6 mice. Gene expression profiles of XMEs were generated using Affymetrix Mouse 430 2.0 arrays for early (GD19, PD7, PD32, PD67) and older (2, 6, 12, 18, 24 months) life stages. Four animals per age group were profiled. Principal component analysis showed a clear age-dependent separation in expression profiles between GD19, PD7 and PD67 hepatic transcripts. Gene expression changes in XMEs were the most dramatic at the early time points (GD19 and PD7) and 24 months. No significant gene changes were observed between 2 and 6 month old mice. We found 365, 286, and 96 XMEs were significantly altered in the GD19, PD7, and PD32 when compared to PD67, respectively. We found 69, 94, and 130 XMEs significantly altered in the 12, 18, and 24 months versus 2 months comparison, respectively. qRT-PCR was performed to confirm altered expression. These data demonstrate dramatic age-dependent changes in XME gene expression in male C57BL/6 mice. Microarray data from this study was compared to other published datasets in dwarf mice (Ames, Little, Snell) and calorically restricted mice. This meta-analysis identified genes altered during "normal" aging, longevity, and caloric restriction.