Diabetes, Vol 40, Issue 11 1375-1381, Copyright © 1991 by American Diabetes Association
New inbred strain of Long-Evans Tokushima lean rats with IDDM without lymphopenia
K Kawano, T Hirashima, S Mori, Y Saitoh, M Kurosumi and T Natori
Tokushima Research Institute, Otsuka Pharmaceutical Company, Japan.
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.