| First Author | Ueda H | Year | 1999 |
| Journal | Diabetes | Volume | 48 |
| Issue | 5 | Pages | 1168-74 |
| PubMed ID | 10331425 | Mgi Jnum | J:55284 |
| Mgi Id | MGI:1337577 | Doi | 10.2337/diabetes.48.5.1168 |
| Citation | Ueda H, et al. (1999) Genetic analysis of late-onset type 2 diabetes in a mouse model of human complex trait. Diabetes 48(5):1168-74 |
| abstractText | 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-1 beta, 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. |
