Selection of mouse strains showing high and low incidences of alloxan-induced diabetes.

To produce an experimental model of diabetes in animals, ICR mice were inbred until the 20th generation by two-way selection toward the high- and low-incidences of alloxan-induced diabetes. Changes in successive generations in the incidence of such diabetes, in blood glucose levels, growth patterns and reproductive performance were studied. The incidence of alloxan-induced diabetes was 41.1% in the basal population; in the high-incidence strain, it was 98.7% in F13, ranging between 90 and 99% in later generations; and in the low-incidence strain, it reached 0% in F7, remaining near that level in later generations. The heritability of the incidence of alloxan-induced diabetes determined at the beginning of selection was 50-60%. The blood glucose level was 251 +/- 19 mg/dl in the basal population; in the high-incidence strain, it was 423 +/- 11 mg/dl in F13, ranging thereafter between 340 and 455 mg/dl; and in the low-incidence strain, it was 128 +/- 4 mg/dl in F7, then varying from 120 to 140 mg/dl in following generations. The heritability of the blood glucose level determined at the beginning of selection was 40-60%. No marked decrease in growth or reproductive performance accompanied successive selections. Successive generations of the high-incidence mice, however, tended to become heavier than the low-incidence animals. The high- and low-incidence strains, established in the 20th generation, were named the ALS (alloxan-induced diabetes-susceptible) and ALR (alloxan-induced diabetes-resistant) strains, respectively.