Genetic analysis of Type 1 Diabetes - Can embryonic stem cells seal the deal?

Nick Holmes and Anne Cooke

Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK

Abstract

The NOD mouse has provided an important animal model for studying the mechanism and genetics of type 1 diabetes over the past 30 years. Arguably the bio-breeding (BB) rat model may be an even closer phenotypic mimic of the typical human disease. Through an extraordinary effort, most conspicuously in the mouse model, a large number of distinct genetic traits which influence diabetes development have been defined. However, in both NOD and BB models the lack of availability of robust means for experimental genetic manipulation has restricted our understanding of the mechanisms underlying these spontaneous autoimmune diseases. Recent developments in the derivation of embryonic stem (ES) cells have the potential to transform this picture. We review here the current state of our understanding of the genetics of type I diabetes in the NOD mouse, the history of the development of ES resources in NOD and the role that ES cells can play in the future in both the NOD mouse and BB rat models.