The discovery and development of the BB rat colony: an animal model of spontaneous diabetes mellitus.

The BB rat model of spontaneous diabetes mellitus was discovered in 1974 in Ottawa in a colony of specific pathogen-free Wistar rats. Investigations to determine the cause of rapid weight loss and death in a few weanling rats from this colony revealed polydypsia, polyuria, glucosuria, ketonuria, and hyperglycemia. These signs regressed and normal weight gain occurred when daily insulin therapy was given. Histologic studies of the pancreas of affected animals showed fibrosis and absence of beta cells. The original colony was established by crossbreeding the clinically normal parents of the diabetic animals. Approximately 10% of the offspring of these matings became diabetic. This incidence was increased to approximately 25% by father-daughter mating, suggesting a genetic component in the etiology.