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.
Mir
Alain A
AA
Laboratory of Metabolism, National Institutes of Health, Baltimore, MD 21224, USA.
Myakishev
Maxim V
MV
Polesskaya
Oksana O
OO
Moitra
Jaideep
J
Petersen
David
D
Miller
Lance
L
Orosz
Andras
A
Vinson
Charles
C
D000818:Animals; D015152:Blotting, Northern; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D008060:Lipodystrophy / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis