Genetically engineered animals carrying defined alterations in their genome can represent invaluable tools for better understanding complex polygenic diseases such as non-insulin-dependent diabetes mellitus (NIDDM) at the molecular level. The structure or expression of a number of genes potentially involved in insulin action or pancreatic beta-cell function have recently been altered in the mouse using transgenic or gene-targeting approaches. The obtention of such mice is the first step towards the development of animal models carrying multiple gene defects which would be very useful in NIDDM research.