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- Title
Genetic analysis of late-onset type 2 diabetes in a mouse model of human complex trait.
- Authors
Ueda, Hironori; Ikegami, Hiroshi; Kawaguchi, Yoshihiko; Fujisawa, Tomomi; Yamato, Eiji; Shibata, Masao; Ogihara, Toshio; Ueda, H; Ikegami, H; Kawaguchi, Y; Fujisawa, T; Yamato, E; Shibata, M; Ogihara, T
- Abstract
Type 2 diabetes is a complex trait with both genes and environmental factors contributing to susceptibility. Except for rare subtypes with monogenic inheritance, the genetic basis of type 2 diabetes is unknown because of the complex and heterogeneous nature of the disease. By using the NSY mouse, an inbred mouse model of type 2 diabetes, we genetically dissected late-onset type 2 diabetes and demonstrated age-dependent changes in the genetic control of type 2 diabetes as well as polygenic inheritance. Three major loci (Nidd1nsy, Nidd2nsy, Nidd3nsy) were mapped on mouse chromosomes (Chr) 11, 14, and 6, respectively. The existence of a fourth locus (Nidd4nsy) with an age-dependent effect was suggested by longitudinal, but not cross-sectional, analysis of linkage data. Nidd1nsy and Nidd4nsy appear to affect insulin secretion, whereas Nidd2nsy and Nidd3nsy appear to affect insulin sensitivity. A locus on Chr 6 was significantly linked to epididymal fat weight. A candidate disease gene (Tcf2) on Chr 11, encoding hepatic nuclear factor-1beta, was shown to have a rare sequence variant in the DNA binding domain in the model. The mouse model we used will serve as a useful model for future studies on the etiology of late-onset polygenic type 2 diabetes in humans.
- Subjects
GENETICS of type 2 diabetes; GLUCOSE tolerance tests
- Publication
Diabetes, 1999, Vol 48, Issue 5, p1168
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.48.5.1168