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Cold Spring Harb Protoc. 2014 Apr 1;2014(4):339-49. doi: 10.1101/pdb.top069807.

Strategies to achieve conditional gene mutation in mice.

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Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Department of Pathology, Harvard Medical School, Charlestown, Massachusetts 02129;


The laboratory mouse is an ideal model organism for studying disease because it is physiologically similar to human and also because its genome is readily manipulated. Genetic engineering allows researchers to introduce specific loss-of-function or gain-of-function mutations into genes and then to study the resulting phenotypes in an in vivo context. One drawback of using traditional transgenic and knockout mice to study human diseases is that many mutations passed through the germline can profoundly affect development, thus impeding the study of disease phenotypes in adults. New technology has made it possible to generate conditional mutations that can be introduced in a spatially and/or temporally restricted manner. Mouse strains carrying conditional mutations represent valuable experimental models for the study of human diseases and they can be used to develop strategies for prevention and treatment of these diseases. In this article, we will describe the most widely used DNA recombinase systems used to achieve conditional gene mutation in mouse models and discuss how these systems can be employed in vivo.

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