A novel model mouse for type 2 diabetes mellitus with early onset and persistent hyperglycemia

Abstract

Various mouse models of type 2 diabetes have been established, but few of these show early onset and persistent hyperglycemia. We have established a congenic mouse strain (NSY.B6-Tyr⁺,A^y) in which a spontaneous mutation of the agouti yellow (A^y) gene, which causes obesity by hyperphagia, was introduced into the NSY strain, which shows increased glucose intolerance with age. This strain has been maintained as a segregating inbred strain by mating obese yellow (A^y/a) males with normal black (a/a) females. All yellow males showed marked obesity and hyperglycemia (mean blood glucose level >400 mg/dl) from 10 to 24 weeks of age. The yellow males also showed glucose intolerance and insulin resistance. They provide a potentially valuable model mouse for research into type 2 diabetes, hyperlipidemia, fatty liver, and renal glomerular complications. Yellow female mice also showed marked obesity, but the incidence of diabetes and the severity of various pathological conditions were milder than in yellow males. None of the black mice showed hyperglycemia in either sex. NSY.B6-Tyr⁺,A^y strain has good fertility and does not display inter-male aggression, making them useful as a new model for type 2 diabetes with early onset and persistent hyperglycemia.