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Genetically Altered Rats

Although historically the focus of much of the research using rats as a model had been on physiological and biochemical arenas because of the larger size of rats, increasingly the resources required to employ rats as a genetically-tractable system have become available. 

 

Chemical mutagenesis strategies

One tool for obtaining genetically altered animals is to treat embryos with a chemical mutagen that causes damage to the DNA.  A frequently used compound for this purpose is N-ethyl-N-nitrosourea (ENU).  A groundbreaking paper demonstrated that this strategy could be employed on rats, and could be used to interfere with genes implicated in cancer, including BRCA1 and BRCA2. 

 

Insertion mutagenesis strategies

Another strategy for developing rats with genome alterations involves insertion of retroviruses and transposable elements. These mobile genetic elements can integrate into the genome and disrupt genes and regulatory regions.  However, due to their non-specific insertional behavior, the results of the integration are not always as desired.

 

Transgenic strategies

Knockout and knockin technologies that are used in the mouse had not been as well developed in the rat initially.  There were transgenic rats developed as early as 1990 using pronuclear injection of DNA constructs. However, the tool kit for generating pluripotent stem cells that are utilized for these strategies in mice were unavailable for rats until more recently. Combined with the opportunity for generating conditional transgenes that can be turned on and off, these techniques will begin to yield more effective models very quickly.

 

Technical aspects

For additional details on the process of generating rat models with genetic modifications, explore the Generating Models Genetic Modifications area of this site.