M-cadherin, a candidate gene for type 2 diabetes and related phenotypes in a KK/Ta mouse model

• Published in: Acta diabetologica Vol. 44; no. 1; pp. 6 - 13
• Main Authors: Shiina, K, Gohda, T, Murakoshi, M, Yamada, K, Aoki, T, Yamazaki, T, Tanimoto, M, Tomino, Y
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01-03-2007
• Subjects: Amino Acid Sequence; Animals; Cadherins - genetics; Cadherins - metabolism; Crosses, Genetic; Diabetes; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Type 2 - genetics; Female; Gene expression; Gene Expression Profiling; Genetic Predisposition to Disease; Genotype & phenotype; Glucose; Male; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Obesity; Phenotype; Rodents; Sequence Homology, Amino Acid
• ISSN: 0940-5429; 1432-5233
• DOI: 10.1007/s00592-007-0234-x

The KK/Ta strain serves as a suitable polygenic mouse model for type 2 diabetes associated with fasting hyperglycaemia, glucose intolerance, hyperinsulinaemia, mild obesity and dyslipidaemia. 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 the gene expression profile in the liver of KK/Ta and BALB/c mice. M-cadherin, a calciumdependent intercellular adhesion molecule, showed increased expression in the liver of KK/Ta mice, and sequence analysis revealed three missense mutations. The relationship between these polymorphisms and various phenotypes in 208 KK/Ta x (BALB/c x KK/Ta) F1 backcross mice was analysed. Statistical analysis revealed that M-cadherin exhibits linkage to levels of triglyceride and insulin in sera, glucose tolerance and body weight. 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 hypertriglyceridaemia, glucose intolerance, hyperinsulinaemia and obesity in KK/Ta mice.