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Aug 2, 2012

Rat Studies Reveal Unexpected Autism Gene Function

  • Researchers at Sigma Advanced Genetic Engineering Labs report that initial studies with their knockout rat autism models at Baylor College of Medicine produced results not seen in other animal models. Citing these results, Sigma and the Autism Speaks® advocacy organization agreed to expand a previous collaboration to develop rat models with modified autism-associated genes.

    The Baylor research, led by Richard E. Paylor, Ph.D., showed that while FMR1 knockout mice exhibit elevated social interactions, rats lacking the same gene participate much less in social play and emit fewer ultrasonic squeaks during play sessions than control rats. These types of social impairments, such as reduced verbal and interactive play, more closely parallel social behavior symptoms seen in humans with FMR1 mutations. Rat models lacking functional NLGN3 and FMR1 genes also display other unexpected characteristics, including compulsive chewing on water bottles and wood blocks. Compulsive and repetitive behaviors are core symptoms in individuals with autism spectrum disorders.

    According to Autism Speaks, an estimated 1 out of 54 boys and 1 in 252 girls are diagnosed with autism in the U.S. The disorder affects over 2 million individuals in the U.S. and tens of millions worldwide.

    Currently SAGE Labs provides the two rat lines with knockouts of autism-associated FMR1 and NLGN3 genes. The remaining five gene knockout rat lines developed in the original collaboration—for the genes MECP2, NRXN1, CACNA1C, PTEN, and MGLUR5—are expected to be released soon, says an official at SAGE. CNTNAP2 and MET knockout rat lines, which will be generated in the expanded collaboration, are expected to be available in 2013.

    "At SAGE Labs we use CompoZr® Zinc Finger Nuclease technology to perform targeted genetic modifications in species previously not amenable to such modifications, be it gene knockout, transgene insertion, point mutations, or conditional gene knockout,” says Edward Weinstein, Ph.D., director of SAGE Labs. “We can help researchers and pharmaceutical companies access rats, rabbits, and other species that best model a medical condition of interest and provide a direct path for preclinical efficacy and toxicology testing,"


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