Genetic engineering as a tool for the generation of mouse models to understand disease phenotypes and gene function

•Overview of the current state of the art in genetic engineering of mouse models.•Current technical difficulties and future developments for further optimization.•Importance of off-target events for the generation of mouse models.

The usage of mouse models has been vital for biomedical research over the last decades, yet the generation of these models has been extremely difficult and labor-intensive. The identification and generation of nucleases able to introduce site-specific DNA double-strand breaks, particularly the CRIPSR/Cas system, is a major breakthrough for this field as the endogenous DNA repair machinery can be hijacked to specifically introduce genome modifications at these sites. This allows for the time-efficient and cost-efficient generation of mouse models by delivery of designer nucleases together with donor DNA into fertilized oocytes.

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