Establishment of two substrains, diabetes-prone and non-diabetic, from Long-Evans Tokushima Lean (LETL) rats

Diabetes mellitus in Long-Evans Tokushima Lean (LETL) rats closely resemble s type 1 diabetes in human beings, e.g., no gender differences in the incid ence of diabetes and no T lymphopenia. Although the LETL rats have been est ablished as an inbred strain, the incidence of diabetes is only similar to 20%. In the present study, we established two substrains, one a diabetes-pr one (KDP) and the other a nondiabetic (KND) from the original inbred LETL r ats. The features of KDP rats are a high incidence of diabetes (over all si milar to 70%) without lymphopenia and 100% development of mild to severe in sulitis at 120-220 days of age. In contrast, the KND substrain is character ized by the complete absence of diabetes incidence. Among 165 SSLP marker l oci throughout all rat chromosomes, no loci showed variation among KDP and KND substrains and their parental LETL rats. In this regard, the genetic ba ckground of these two substrains, KDP and KND, appears to be uniform except for the major gene(s) that is responsible for the diabetes. In this contex t, these two substrains of LETL rats should serve as useful tools for resea rch on the pathogenesis and for the genetic analysis of type 1 diabetes. In this report, we have not only established, but also characterized these tw o substrains, and provided their fundamental data.