Rat models

Animal models continue to be important tools for understanding disease mechanisms and for preclinical testing of potential therapeutics. Although the mouse is currently the most widely used species to model neurobiological disorders, we recognize that other model systems may also provide important insights.

Prior to the advent of targeted mutagenesis using mouse embryonic stem cells, the rat was the animal of choice in neurobiology. The rat shows a more complex behavioral repertoire than the mouse, and its larger brain permits more sophisticated electrophysiological recordings. Rats are sometimes falsely perceived as slightly larger versions of mice; however, the evolutionary distance between rats and mice may be as great as that between humans and Old World monkeys1. Recent developments in genomic-editing technologies have facilitated the ability to manipulate the rat genome, thus renewing interest in the rat as a model for genetically linked disorders.

As such, SFARI is working with the Medical College of Wisconsin (MCW) to generate and distribute CRISPR/Cas9 rat models of autism. Models will be maintained in the outbred Long-Evans background strain, as this is often the strain of choice for cognitive, behavioral and systems neuroscience studies. The intent is for these models to be available to any qualified researcher, with minimal cost and restrictions.

Available (or soon to be available) rat models

  • Fmr1 knockout
  • Arid1b deletion*
  • Grin2b deletion*
  • Dyrk1a deletion*

*Contact the MCW Gene Editing Rat Resource Center for more information: mcwcustomrats@mcw.edu.

Furthermore, as an initial effort to characterize these lines, rats will be behaviorally phenotyped by Peter Kind and colleagues at the University of Edinburgh in collaboration with Sumantra “Shona” Chattarji and his team at the Center for Development and Repair in Bangalore. Resulting data will be available to the community in a timely manner.

Future rat models

SFARI plans to develop additional rat models based on recently identified high-confidence autism risk genes.  Constitutive knockouts for Scn2a and 16p11.2 deletion may be available in late 2019.

Our overriding goal is to make available to the research community autism rat models of the highest value, so please feel free to contact us for further information on specific lines, as well as suggestions and comments on our efforts more generally: models@simonsfoundation.org.

 

Image Credit: Jason Snyder/flickr

 

References

1.Gibbs R.A. et al. Nature 428, 493-521 (2004) PubMed
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