Genetic modifier screens in mice

ENU mutagenesis is a forward genetics strategy in which random mutagenesis and phenotypic screening is used to identify genes based on the phenotype induced when they are mutated. A modifier screen is a type of screen in which mice with a pre-existing phenotype are utilized to identify mutations that can enhance or suppress this phenotype. This approach has the potential to uncover missing pathway members, reveal novel genetic interactions, and pinpoint new drug targets. Considerations when planning a suppressor screen include current knowledge, genomic footprint, penetrance, variance, robustness, latency of the starting phenotype, viability, fertility, genetic background and ENU tolerance of starting strain, screening assay, mouse numbers required, and mutation identification strategy. Practical advice on each of these is provided in this review. Curr. Protoc. Mouse Biol. 2:75-87 ? 2012 by John Wiley Sons, Inc.