The TALLYHO Mouse as a Model of Human Type 2 Diabetes

Abstract

The TALLYHO/Jng (TH) mouse is an inbred polygenic model for type 2 diabetes (T2D) with moderate obesity. Both male and female TH mice are characterized by increased body and fat pad weights, hyperlep-tinemia, hyperinsulinemia, and hyperlipidemia. Glucose intolerance and hyperglycemia are exhibited only in males. Reduced 2-deoxy-glucose uptake occurs in adipose tissue and skeletal muscle of male TH mice. While both sexes of TH mice exhibit enlarged pancreatic islets, only males have degranulation and abnormal architecture in islets. Endothelial dysfunction and considerably decreased bone density are also observed in male TH mice. The blood pressure of male TH mice is normal. Genetic outcross experiments with non-diabetic strains revealed multiple susceptibility loci (quantitative trait loci) for obesity, hypertriglyceri-demia, hypercholesterolemia, and hyperglycemia. In conclusion, TH mice encompass many aspects of polygenic human diabetes and are a very useful model for T2D.