Collaboration Leads to Promising Rat Models of Autism

The importance of the rat in modern research cannot be underestimated. The rat has been one of the most preferred animal models due to its size and similarities to human physiology and socialization habits. However, genetic studies have traditionally been the domain of the mouse due to the ease with which the mouse genetic code can be manipulated. While the techniques used for genetic manipulation in the mouse were developed decades ago, genetic alteration of the laboratory rat has only recently been achieved.

The sequencing of the genome of the Brown Norway rat in 2004 (Lindblad-Toh 2004) was an achievement that opened up possibilities for new discoveries and potential treatments of many diseases and disorders with a possible genetic component. The rich knowledge that already existed from previous work in rats could now be developed further by gene manipulation (Jacob and Kwitek 2002). A promising collaboration between Sigma Advanced Genetic Engineering Laboratories (SAGE® Labs) and Autism Speaks® is building on decades of existing autism knowledge through just this type of gene manipulation (Jacob and Kwitek 2002).

Autism, also known as autism spectrum disorder, affects an estimated 1.5 million Americans and is characterized by difficulty with communication, reduced social interaction skills, and involvement in repetitive behaviors. Although there has been strong evidence of a genetic basis for these symptoms using mice in autism research has proven limited due to the animals’ limited cognitive abilities and reduced number of behavioral patterns, deficits which would be alleviated by the development of appropriate rat models.

The goal of the initial collaboration between these two groups was to generate gene knockout rats, inactivating or mutating specific genes, such as FMR1 or NLGN3, thought to play a role in human autism. Using their own Zinc Finger Nuclease® technology to achieve genetic manipulation in rats, SAGE Labs has developed seven lines of knockout rats, two of which are publicly available and show characteristic behaviors of autism. In particular, the juvenile FMR1 knockout rat displays decreased socialization as evidenced by decreased ultrasonic vocalizations and a decrease in interactive play. FMR1 is a mutated gene sometimes seen in humans with autism.

This collaboration has proceeded well enough that SAGE Labs and Autism Speaks have announced an expanded collaboration to create more genetically modified rat models of autism, focusing on additional genes including CNTNAP2 and MET.

We wish both SAGE® Labs and Autism Speaks® the best of luck in this ambitious project, and are excited to see the results!

Further Reading:

“SAGE® Labs and Autism Speaks Expand Collaboration to Develop Rat Models for Translational Autism Research.” Sageresearchmodels.com. August 2, 2012.

“Rats Rising: Using the Rat as a Model Organism for Autism Research.” blog.autismspeaks.org. October 28, 2010.

Lindblad-Toh K. Genome sequencing: Three’s company. Nature. (2004). 428(428) 475-476.

Jacob HJ, Kwitek AE. Rat genetics: attaching physiology and pharmacology to the genome. (2002). Jan;3(1):33-42.