Rat knockout and mutant models

The development of rat genetic models has rapidly progressed over the past decades and has become an important strategy to connect gene function to various aspects of health and disease. Reverse genetics or gene-driven genetics is a broadly accepted approach to study gene function. An indispensable reverse genetic tool is the generation and characterization of knockout and mutant animals for the genes of interest. Recently, the laboratories of Dr. Michael Gould (Madison, WI) and Dr. Edwin Cuppen (Utrecht, The Netherlands) have independently developed methods using N-ethyl-N-nitrosourea (ENU) mutagenesis to make rat knockouts and mutants in any gene of interest. This chapter describes experienced-based considerations from both laboratories that could serve as a guideline for initiating ENU mutagenesis-based screens in the rat.