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Microarray Analysis of Gene Expression in the Kidneys of New- and Post-Onset Diabetic NOD Mice

¹ Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, Georgia
² Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida
³ North Florida/South Georgia Veterans Health System, Gainesville, Florida

We profiled the expression of 5,760 clones from a kidney subtraction library in the kidneys of three groups of NOD mice: nondiabetic, new-onset, and long-term diabetic. A total of 27 genes had lower expression and 1 gene (Gpx3) had higher expression in the new-onset diabetic mice compared with nondiabetic control NOD mice (P < 0.001). Similarly, 19 of the above 27 genes and 7 additional genes had higher expression and the Gpx3 gene had lower expression in long-term diabetic mice compared with controls (P < 0.001). Interestingly, only three genes may be different between new-onset and long-term diabetic mice (P < 0.0004). These genes are from diverse functional groups, including oxidative phosphorylation, free radical neutralization, channels, pumps, lipid processing, transcription and translation machinery, protein trafficking, constitutive protein processing, and immune function. The majority of these genes fall into four signaling pathways: insulin, transforming growth factor-ß, tumor necrosis factor-, and peroxisome proliferator–activated receptor. The most significant expression change was found for the stearoyl-coenzyme A desaturase 1 (SCD1) gene (P < 10^-7). The lower expression levels of the SCD1 gene in both diabetic groups compared with controls were further confirmed by Northern blot analysis and immunohistochemistry.

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