Tuesday, August 22, 2006

Autoimmune Diabetes: Gene expression changes little in diabetic mouse

drj writes "More than 20 genes are known to influence the development of type 1 (autoimmune) diabetes in mice and at least this number are thought to contribute to the disease in humans. Using microarrays representing over 39,000 transcripts, Eaves et al. compared mice from closely related lines that do, or do not, develop diabetes. They identified over 400 differentially expressed genes in spleen and thymus tissues and 8 candidates for one particular susceptibility locus (Idd9.1). However, the expectation that the susceptibility (Idd) loci cause large scale differences in gene expression proved to be wrong. Instead, few changes were observed, suggesting that general patterns of gene expression resist change even during the development of a serious autoimmune disease.
To avoid excluding “suggestive” changes, the investigators set the level of significant change at 1 per 20,000 transcripts instead of 1 per 20 arrays (~800,000 transcripts). They identified potential cis-acting changes by examining chromosome locations. For example, the Idd3 region derived from B6 mice protects about 2/3 of NOD mice from diabetes (20-25% vs. 75-80%). However, only 8 transcripts change expression in Idd3B6 mice, all only modestly (19-66%), and none map within the 0.35 cM Idd3 region on chromosome 3."
PubMed Eaves IA, Wicker LS, Ghandour G, Lyons PA, Peterson LB, Todd JA, Glynne RJ., Combining Mouse Congenic Strains and Microarray Gene Expression Analyses to Study a Complex Trait: The NOD Model of Type 1 Diabetes. Genome Res. 2002;12:232-242"

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