Features and Strategies of ENU Mouse Mutagenesis

Dian      Soewarto; Matthias      Klaften; Isabel      Rubio-Aliaga

Abstract

Aim of this review is to demonstrate the relevance of animal models created by ENU mutagenesis for the pharmaceutical community to understand diseases and the modulation of disease status by pharmaceutical compounds. We give an overview of what ENU mutagenesis in mice implies and introduce the main research centers running ENU mutagenesis projects. The different strategies of ENU mutagenesis screens are explained as well as the latest advances in mapping and mutation detection strategies, which until recently have been the main limiting step in forward genetics/ phenotype- driven approaches. ENU mutagenesis in mice has shown its power by providing animal models for human monogenic diseases. Moreover, the development of modifier and sensitized screens extended this resource to models for multigenic diseases and thereby opened the perspective to understand the modulation of disease states. Finally, we provide information about the accessibility and availability of these models for academic research.

Keywords: ENU mutagenesis, allelic series, sensitized screen, modifier screen, SNP mapping, animal disease model, target validation, drug development