Uncovering the uncharacterized and unexpected: Unbiased phenotype‐driven screens in the mouse

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Abstract
Phenotype‐based chemical mutagenesis screens for mouse mutations have undergone a transformation in the past five years from a potential approach to a practical tool. This change has been driven by the relative ease of identifying causative mutations now that the complete genome sequence is available. These unbiased screens make it possible to identify genes, gene functions and processes that are uniquely important to mammals. In addition, because chemical mutagenesis generally induces point mutations, these alleles often uncover previously unappreciated functions of known proteins. Here we provide examples of the success stories from forward genetic screens, emphasizing the examples that illustrate the discovery of mammalian‐specific processes that could not be discovered in other model organisms. As the efficiency of sequencing and mutation detection continues to improve, it is likely that forward genetic screens will provide an even more important part of the repertoire of mouse genetics in the future. Developmental Dynamics 235:2412–2423, 2006.

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