Creating a “Hopeful Monster”: Mouse Forward Genetic Screens

Abstract

One of the most straightforward approaches to making novel biological discoveries is the forward genetic screen. The time is ripe for forward genetic screens in the mouse since the mouse genome is sequenced, but the function of many of the genes remains unknown. Today, with careful planning, such screens are within the reach of even small individual labs. In this chapter we first discuss the types of screens in existence, as well as how to design a screen to recover mutations that are relevant to the interests of a lab. We then describe how to create mutations using the chemical N-ethyl-N-nitrosourea (ENU), including a detailed injection protocol. Next, we outline breeding schemes to establish mutant lines for each type of screen. Finally, we explain how to map mutations using recombination and how to ensure that a particular mutation causes a phenotype. Our goal is to make forward genetics in the mouse accessible to any lab with the desire to do it.