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Diabetes 53:366-375, 2004
© 2004 by the American Diabetes Association, Inc.

Gene Expression Profiles Define a Key Checkpoint for Type 1 Diabetes in NOD Mice

Sarah E. Eckenrode, Qingguo Ruan, Ping Yang, Weipeng Zheng, Richard A. McIndoe, and Jin-Xiong She

From the Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, Georgia

cDNA microarrays with >11,000 cDNA clones from an NOD spleen cDNA library were used to identify temporal gene expression changes in NOD mice (1–10 weeks), which spontaneously develop type 1 diabetes, and changes between NOD and NOD congenic mice (NOD.Idd3/Idd10 and NOD.B10Sn-H2b), which have near zero incidence of insulitis and diabetes. The expression profiles identified two distinct groups of mice corresponding to an immature (1–4 weeks) and mature (6–10 weeks) state. The rapid switch of gene expression occurring around 5 weeks of age defines a key immunological checkpoint. Sixty-two known genes are upregulated, and 18 are downregulated at this checkpoint in the NOD. The expression profiles are consistent with increased antibody production, antigen presentation, and cell proliferation associated with an active autoimmune response. Seven of these genes map to confirmed diabetes susceptibility regions. Of these seven, three are excellent candidate genes not previously implicated in type 1 diabetes. Ten genes are differentially expressed between the NOD and congenic NOD at the immature stage (Hspa8, Hif1a, and several involved in cellular functions), while the other 70 genes exhibit expression differences during the mature (6-10 week) stage, suggesting that the expression differences of a small number of genes before onset of insulitis determine the disease progression.

Address correspondence and reprint requests to Dr. Jin-Xiong She Center for Biotechnology and Genomic Medicine, Medical College of Georgia, 1120 15th Street, PV6B108, Augusta, GA 30912-2400. E-mail: jshe{at}mail.mcg.edu


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.