Pathophysiology and genetics of obesity and diabetes in the New Zealand obese mouse: a model of the human metabolic syndrome

Abstract

The New Zealand Obese (NZO) mouse is one of the most thoroughly investigated polygenic models for the human metabolic syndrome and type 2 diabetes. It presents the main characteristics of the disease complex, including early-onset obesity, insulin resistance, dyslipidemia, and hypertension. As a consequence of this syndrome, a combination of lipotoxicity and glucotoxicity produces beta-cell failure and apoptosis resulting in hypoinsulinemia and diabetic hyperglycemia. With NZO as a breeding partner, several adipogenic and diabetogenic gene variants have been identified by hypothesis-free positional cloning (Tbc1d1, Zfp69) or by combining genetic screens and candidate gene approaches (Pctp, Abcg1, Nmur2, Lepr). This chapter summarizes the present knowledge of the NZO strain and describes its pathophysiology as well as the known underlying genetic defects.