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.

Fragile X rat model

A rat model of fragile X syndrome (FMR1 knockout) is the first of these models to be generated through this collaboration, and is now available for ordering from MCW. This model is on the outbred Long-Evans background strain and the construct mimics previous models made in the mouse2 and in the Sprague-Dawley rat strain.

Interested researchers should contact the MCW Gene Editing Rat Resource Center for more information: mcwcustomrats@mcw.edu

Furthermore, as an initial effort to characterize this line, FMR1 KO rats will be behaviorally phenotyped in collaboration with the University of Edinburgh and 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 five additional rat models based on recently identified high-confidence autism risk genes: ARID1B, CHD8, DYRK1A, GRIN2B and SCN2A. We will attempt to generate these as conditional loxP models. These models are expected to be available in 2018.

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

 

References

  1. 1.Gibbs R.A. et al. Nature 428, 493-521 (2004) PubMed
  2. 2.The Dutch-Belgian Fragile X Consortium, Cell 78, 23-33 (1994) PubMed
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