The Spontaneously Diabetic BB Rat: Sites of the Defects Leading to Autoimmunity and Diabetes Mellitus. A Review

Abstract

The spontaneously diabetic BB rat, discovered serendipitously in 1974 in a commercial breeding facility (Bireeding Laboratories, Ottawa, Ontario), is an animal model that displays clinical and pathologic features closely resembling Type 1 (insulin-dependent, juvenile-onset) diabetes meilitus in humans. In both diseases, an immune pathogenesis appears to contribute to the destruction of the pancreatic beta cells. Since first described by NAKHOODA and coworkers (NAKHOODA et al. 1977), the BB rat diabetic syndrome has been extensively characterized. The syndrome is manifest by an abrupt onset of severe hyperglycemia secondary to insulinopenia, with a lymphocytic and monocytic infiltration of the pancreatic islets (insulitis) before and during the acute phase of hyperglycemia (LIKE et al. 1982a; MARLISS et al. 1982; LIKE and ROSSINI 1984; YALE and MARLISS 1984). Genetically susceptible male and female rats develop hyperglycemia with equal frequency and severity, with the time of onset varying from approximately 60 to 120 days of age. Peak onset of diabetes occurs around the age of sexual maturation (80–100 days); the frequency of diabetes in untreated BB rats less than 60 days of age is 0.5% (LIKE and ROSSINI 1984). Characteristically, the animals are nonobese, and diabetic animals require daily insulin injections to prevent ketoacidosis and death. As in humans, the diabetic syndrome has been shown to be associated with genes in the major histocompatibility complex (MHC) (COLLE et al. 1981; JACKSON et al. 1984). No known pathogens have been implicated; the syndrome occurs with equal frequency and severity in animals raised in a pathogen-free environment (ROSSINI et al. 1979).