Identification of the diabetogenic gene and its related genes of high fat diet-induced diabetes by using novel mouse model

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SMXA-5 mouse is a novel animal model for type 2 diabetes induced by high fat diet-feeding. We have mapped the diabetic QTL (quantitative trait locus:T2dm2sa) on chromosome 2 of SMXA-5 mouse. The aim of this study is to choose the candidate gene for this diabetogenic gene and identify it as a causative gene. Simultaneously, the controlled genes by the isolated gene, which contribute to the development of diabetes,were screened.The chromosomal region which this diabetogenic gene exists was narrowed to 5Mb region of chromosome 2 by the phenotipic analyses of several diabetic congenic strains. As a candidate gene, Rapgef 4 was chosen. In the exon of Rapgef4 of SMXA-5 mouse, we observed a mutation causing the amino acid substitution. Further study is needed to clarify that this mutation of rapgef4 caused the development of diabetes.