e wealth of information collected on the rat to date, these emerging tools are boosting the significance of the rat as an animal model. All together, these techniques have opened the door for new possibilities with the premise of creating more predictive models, which could reduce drug development costs and increase success rates.
Two companies—Transposagen Biopharmaceuticals and Sigma-Aldrich Advanced Genetic Engineering (SAGE™) Labs—have already begun creating and distributing knockout rat disease models. Transposagen, using mobile DNA technology, has made available to the research community over 100 unique knockout lines, and is planning to produce 30,000 unique knockout rat lines in all.
SAGE is using ZFN technology, which generates site-specific, double-stranded breaks in the genome, to create knockout rats for a variety of conditions including diabetes, Parkinson disease, and Alzheimer disease. The firm recently announced a collaboration with the Michael J. Fox Foundation to create a model more representative of human Parkinson disease in the rat.
Will the Rat Really Replace the Mouse?
Genetically engineered rat models could potentially overcome the shortcomings associated with mouse morphology and physiology and, in the years to come, make the rat the model of choice for elucidating gene function and decoding physiological processes. But what practical barriers exist in transitioning to the rat, and how long will it take for knockout rats to be fully embraced by the biomedical community?
While the rat may be the preferred rodent in many contexts, logistical challenges including animal facility setup, housing space constraints, and other financial considerations may slow acceptance of the knockout rat as a mouse alternative.
The scientific community will need to weigh these considerations against the incremental value a disease model in a rat background may provide. Similar to other tools, industry acceptance of genetically engineered rats will require time to develop models, publish results, prove the utility of a model, and garner acceptance from regulatory authorities.
While the rat may offer an improved platform when compared to the mouse in many cases, availability, production throughput, and costs will all play a role in determining how widespread the use of knockout rats will become.
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