A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Winter, 2017 | Number 1, Volume 31

Lack of single protein may cause a third of cases of ASD

As many as one-third of cases of autism spectrum disorder (ASD) may involve a shortage of a single protein in the brain, according to researchers at the University of Toronto. Earlier research by Mathieu QuesnelVallières and colleagues demonstrated that the protein, called nSR100, is reduced in the brains of individuals with ASD. In the new study, the researchers genetically engineered mice with reduced levels of this protein. The mice developed autistic-like behaviors, including avoidance of social interaction and heightened sensitivity to noise. “We previously reported an association between nSR100 protein levels and autism,” study coauthor Sabine Cordes says. “But this time we show that reduced levels of this protein could really be causative—that’s a big deal. Just by reducing the nSR100 levels by 50%, we observe hallmarks of autistic behavior.” In the brain, nSR100 is a key regulator of alternative splicing, which involves removing non-coding DNA and bringing protein-coding segments together to make a finished protein template. The researchers speculate that autism stems in part from an accumulation of incorrectly spliced proteins in brain cells, resulting in errors in brain wiring. They detected changes in alternative splicing and brain wiring in their nSR100-deficient mice. Cordes says, “Instead of focusing on individual mutations linked to autism, it’s much more powerful to identify regulatory hubs like nSR100. In the future, if you turned this protein up a little bit in autistic patients, you might be able to improve some of the behavioral deficits.” 


“Misregulation of an activity-dependent splicing network as a common mechanism underlying autism spectrum disorders,” Mathieu Quesnel-Vallières, Zahra Dargaei, Manuel Irimia, Thomas Gonatopoulos-Pournatzis, Joanna Y. Ip, Mingkun Wu, Timothy Sterne-Weiler, Shinichi Nakagawa, Melanie A. Woodin, Benjamin J. Blencowe, and Sabine P. Cordes, Molecular Cell, Vol. 64, No. 6, pp. 1023-34, December 15, 2016. Address: Benjamin Blencowe, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada, [email protected]


“U of T researchers make autism breakthrough,” Jovana Drinjakovic, University of Toronto, December 15, 2016.