A female mouse spontaneously exhibiting polyuria and glucosuria accompanied by rapid weight loss was found in one of two sublines derived from the CTS mice. Eight mating pairs were made using its offspring and selection was performed for both spontaneous diabetes and reproductive ability. After six generations of the selective breeding the diabetic (nod) and the control (non) lines were established.
A marked sex difference was observed in the incidence of diabetic symptoms in the nod mouse. The cumulative incidence of the onset up to 30 weeks of age was 80% in females and less than 20% in males. The onset of diabetes was abrupt in both sexes, and spontaneous remission was not observed. However, daily administration of insulin induced an increase of body weight and a prolongation of life span.
Diabetic symptoms are biochemically characterized by polyuria, polydipsia, hyperglycemia, glucosuria and hypercholesteremia. Pathological examination revealed a high frequency of lymphocyte infiltration around and/or into the Langerhans' islet. It was observed even at the prediabetic stage over five weeks of both sexes. The number and size of the islets were markedly reduced in the overt diabetic mice.
Although the mechanism of the pathogenesis is not clear yet, the nod mouse may be a useful animal model for investigating the human juvenile type diabetes.