New inbred strain of Long-Evans Tokushima lean rats with IDDM without lymphopenia.

Spontaneously diabetic rats with remarkable polyuria, polyphagia, and polydipsia were discovered in 1983 in an outbred colony of Long-Evans rats purchased from Charles River Canada in 1982. They have since been maintained at the Tokushima Research Institute (Otsuka Pharmaceutical, Tokushima, Japan). A strain of rats (Long-Evans Tokushima Lean [LETL]) with diabetes was bred from these rats. The characteristic features of the disease in LETL rats are 1) sudden onset of polyuria, polyphagia, hyperglycemia, and weight loss; 2) no sex differences in the rate of onset or severity; 3) lymphocyte infiltration into islets followed by destruction of beta-cells and disappearance of lymphocytes at the onset of diabetes; 4) no significant T lymphopenia; 5) lymphocyte infiltration into the salivary glands and lacrimal glands; and 6) at least two recessive genes involved in the pathogenesis of insulitis, one of which is closely linked with RT1u. These characteristics closely resemble those of human insulin-dependent diabetes mellitus (IDDM). Results suggest that the LETL rat is a useful animal model for analysis of genetic and immunologic factors relating to the pathogenesis of human IDDM.