Biological and behavioural characterisation of rats genetically engineered to model autism

The biological and behavioural characterisation of the first rats genetically engineered to model autism have been released by Sigma Advanced Genetic Engineering (SAGE) Labs, an initiative of Sigma Life Science, in partnership with Autism Speaks.

The novel rat models of autism mimic specific symptoms and pathologies of autism to provide an unprecedented opportunity to investigate the underlying biology and therapeutic targets for autism spectrum disorders.

Autism affects tens of millions of people worldwide, with US government statistics suggesting diagnoses are increasing annually by 10 to 17%. The cause and underlying neurobiology of autism remains poorly understood. Strong evidence does exist for a genetic basis of autism, prompting development of mice that model the genetic mutations found in autistic humans. However, the mouse’s utility for autism research is restricted because the species’ limited cognitive abilities and small behavioural repertoire often do not adequately reflect the behaviours or biology of humans with autism.

“The robust behavioural repertoire, similarities with human physiology and sheer size contrast with mice, making rats an attractive model species for investigating neurodevelopmental disorders like autism,” said Robert Ring, PhD, Vice President of Translational Research at Autism Speaks, who added, “Developing these genetic models in rats has additional advantages from a translational research perspective in that they enable investigators to study the effects of novel treatments on autism relevant phenotypes in the same species traditional pharmacokinetics, metabolism and toxicology are studied to support the drug development process.”

The knockout autism model rats were co-developed in a collaboration between scientists at SAGE Labs and Autism Speaks. The rats mimic specific symptoms of autism spectrum disorder because they are each genetically engineered to lack one of seven genes associated with the autism spectrum disorders: Fmr1, Neuroligin 3, Neurexin 1 alpha, Cav1.2, MeCP2, mGluR5, or PTEN. These rats will be available to all researchers through SAGE Labs by early 2012.

Scientists at SAGE Labs created the transgenic autism model rats through the SAGEspeed model creation process, which uses Sigma’s CompoZr zinc finger nuclease (ZFN) technology. CompoZr ZFN technology enables highly efficient, targeted editing of the genome of any species - previously impossible for complex species other than mice.

“One can use CompoZr ZFN technology to rapidly generate a genetic disease model in the species that is the best model for that condition, instead of relying only upon the mouse,” said Edward Weinstein, PhD, Director of SAGE Labs.

In a separate collaboration with The Michael J Fox Foundation, scientists at SAGE Labs created transgenic rats that are the first animal models of Parkinson’s disease to tremor as humans do. Other transgenic research models created by SAGE Labs include rats for Alzheimer’s, schizophrenia, cancer and cardiovascular disease research, as well as rats for toxicology testing in drug development.

SAGE Labs’ model generation services are available for rats, mice, rabbits and other organisms.

For more information, visit www.sageresearchmodels.com.