A search for candidate genes for lipodystrophy, obesity and diabetes via gene expression analysis of A-ZIP/F-1 mice.

Genome scans for diabetes have identified many regions of the human genome that correlate with the disease state. To identify candidate genes for type 2 diabetes, we examined the transgenic A-ZIP/F-1 mouse. This mouse model has no white fat, resulting in abnormal levels of glucose, insulin, and leptin, making the A-ZIP/F-1 mice a good model for lipodystrophy and insulin resistance. We used cDNA-based microarrays to find differentially expressed genes in four tissues of these mice. We examined these results in the context of human linkage scans for lipodystrophy, obesity, and type 2 diabetes. We combined 199 known human orthologs of the misregulated mouse genes with 33 published human genome scans on a genome map. Integrating expression data with human linkage results permitted us to suggest and prioritize candidate genes for lipodystrophy and related disorders. These genes include a cluster of 3 S100A genes on chromosome 1 and SLPI1 on chromosome 20.