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Over-produced autism gene alters synapses, affects learning and behavior in mice
Date:6/5/2013

EUGENE, Ore. -- (June 5, 2013) -- A gene linked to autism spectrum disorders that was manipulated in two lines of transgenic mice produced mature adults with irreversible deficits affecting either learning or social interaction.

The findings, published in the May 29 issue of the Journal of Neuroscience, have implications for potential gene therapies but they also suggest that there may be narrow windows of opportunity to be effective, says principal investigator Philip Washbourne, a professor of biology and member of the University of Oregon's Institute of Neuroscience.

The research, reported by an 11-member team from three universities, targeted the impacts of alterations in the gene neuroligin 1 -- one of many genes implicated in human autism spectrum disorders -- to neuronal synapses in the altered mice during postnatal development and as they entered adulthood. One group over-expressed the normal gene, the other a mutated version.

Mice with higher-than-normal levels of the normal gene after a month had skewed synapses at maturity. Many were larger, appearing more mature, than normal. In these mice, Washbourne said, there were clear cognitive problems. "Behavior was just not normal. They didn't learn very well, and they were slower to learn, but their social behavior was not impacted."

Mice over-producing a mutated version of the gene reached adulthood with structurally immature synapses. "They were held back in development and behavior -- the way they behave in terms of learning and memory, in terms of social interaction," he said. "These were adult mice, three months old, but they behaved like normal mice at four weeks old. We saw arrested development. Learning is a little bit better, they are more flexible just like young mice, they learn faster, but their social interaction is off. To us, this looked more like Asperger's syndrome.

"So with the same gene, doing two different manipulations -- overexpres
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Contact: Jim Barlow
jebarlow@uoregon.edu
541-346-3481
University of Oregon
Source:Eurekalert

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