The Simons Foundation Autism Research Initiative (SFARI) is pleased to announce that eight genetic rat models of autism spectrum disorder (ASD) are now available from the Medical College of Wisconsin (MCW). These models were generated using CRISPR/Cas9 genome-editing techniques and being maintained in the outbred Long-Evans background strain. The intent is for these models to be available to any researcher, with minimal cost and restrictions. In addition, these models are being behaviorally phenotyped through a partnership with the Simons Initiative for the Developing Brain (SIDB). Resulting data are available prepublication to any interested researcher.

Available models

Available rat models include:

• Arid1b knockout
• Chd8 knockout
• Cntnap2 knockout
• Dyrk1a knockout
• Fmr1 knockout
• Grin2b knockout
• Nrxn1 knockout
• Scn2a knockout

SFARI selected these models based on the strength of the human genetic evidence supporting the role of these genes in ASD risk, as well as the availability of other SFARI-supported experimental models of these genes (see below for further details). SFARI chose to generate these models on the outbred Long-Evans background, as we recognized the dearth of availability of autism rat models on the preferred strain for systems neuroscience studies.

More information on these models can be found on the rat models page on SFARI.org and relevant pages on the MCW-Rat Genome Database (RGD) website.

Behavioral characterization

As an initial effort to characterize these lines, rats are being behaviorally phenotyped through a partnership with SIDB, at the University of Edinburgh and the Center for Brain Development and Repair (CBDR) in Bangalore.

The SIDB/CBDR behavioral pipeline is a systematic, rigorous platform consisting of tasks specifically chosen based on known circuit biology to ensure coverage of a large number of brain regions. Results of behavioral studies will be available prepublication as data sheets posted on the SFARI and MCW-RGD websites.

The Fmr1 knockout rat data sheet is now accessible for download, with additional data sheets forthcoming as validated results become available. SFARI hopes that such data will help to set the stage for other investigators to perform more in-depth studies on these models.

Access to these models

Researchers interested in studying these models should contact the MCW Gene Editing Rat Resource Center directly to obtain access: mcwcustomrats@mcw.edu.

Other relevant models

In addition to rat models, SFARI has facilitated the creation of other experimental systems for studying ASD, including mouse, zebrafish and human induced pluripotent stem cell (iPSC) models.

Models for several of the high-confidence ASD genes now exist across multiple experimental platforms, making comparative studies possible. Identifying cellular, circuit or behavioral phenotypes that are conserved across species may help shed light on fundamental aspects of ASD biology. Studies using a variety of different models of the same genetic risk factor are also likely to improve the predictive validity of preclinical investigations for therapeutic development.

“We are thrilled that these rat models and their associated data are now available to the research community,” says SFARI senior scientist Alice Luo Clayton. “Our hope is that by providing preferred reagents and foundational knowledge to the scientific community, more researchers will be interested in studying questions of importance for autism. Similarities and differences between mouse and rat models of the same ASD risk gene have already been observed in a number of studies (e.g., for Fmr1¹), highlighting the importance of rigorous studies at multiple levels of analysis across multiple species.”

1. Till S.M. et al. Hum. Mol. Genet. 24, 5977-5984 (2015) PubMed