Objective : The KK/Ta strain serves as a suitable polygenic mouse model for type 2 diabetes associated with fasting hyperglycemia, glucose intolerance, hyperinsulinemia, mild obesity and dyslipidemia. Recently, we reported the susceptibility loci contributing to type 2 diabetes and related phenotypes in KK/Ta mice. In the present study, to identify susceptibility genes for type 2 diabetes and related disorders, GeneChip Expression Analysis was employed to survey gene expression profiles in the liver of KK/Ta and BALB/c mice. Materials and Methods : Livers from KK/Ta and BALB /c mice at 20 weeks of age were disected. Total RNA was extracted and labeled for hybridizing to the Affymetrix Murine Genome U74Av2 array. Genes that were differentially expressed between KK/Ta and BALB / c mice were confirmed by RT-PCR analysis and direct sequencing was performed. The relationship between polymorphisms and various phenotypes in 208 KK/Ta × (BALB / c × KK/ Ta) F1 backcross mice was analyzed. Results : M-cadherin showed increased expression in the liver of KK/Ta mice by GeneChip analysis. M-cadherin mRNA levels were increased in the liver and muscle of KK/Ta mice by RT-PCR analysis and sequence analysis demonstrated three missense mutations. Statistical analysis of the relationship between polymorphisms and phenotypes in backcross mice demonstrated that M-cadherin exhibits linkage to levels of triglyceride and insulin in sera, glucose tolerance and body weight. Conclusions : Although it has been postulated that M-cadherin may be important for the regulation of morphogenesis of skeletal muscle cells, these results suggest that M - cadherin may influence hypertriglyceridemia, glucose intolerance, hyperinsulinemia and obesity, a constellation of symptoms called Metabolic syndrome in KK/Ta mice.