Hereditary diabetes in the KK mouse: an overview

Abstract

Table III compares metabolic and morphologic characteristics of different species of control and KK mice. The C57BL/6J demonstrates no significant metabolic, clinical or histologic abnormalities. Our two highly inbred Swiss albino groups I and II also do not show significant glomerular lesions, although we found striking intolerance to glucose, hyperinsulinism, and obesity among them. Thus a genetic predisposition may be necessary in addition to various environmental factors to produce microangiopathy in KK mice. The yellow AY mouse is included in this table, since it is strikingly hyperinsulinemic and obese without concomitant vasculopathy such as the other mentioned control strains have. In conclusion, the KK mice develop chemical diabetes preceded by a stage of prediabetes and also demonstrate renal, retinal and neurologic complications similar to those seen in human diabetes. Of particular interest is the development of mild to moderate glomerulosclerosis in the prediabetic stage; with progression to severe glomerulosclerosis and attendant proteinuria later in life. With proper back-crossing, both hyperglycemia and glomerulosclerosis can be transmitted to normal control mice, suggesting that a specific genetic background is necessary for the development of diabetes and diabetic-like microangiopathy. We therefore suggest that the KK mouse serves as an ideal genetic animal for the study of non-insulin-dependent diabetes mellitus and its complications for rational prevention and therapy.