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Study links enzyme to autistic behaviors
Date:7/23/2014

table, which leads to functional deficits that depend on where in the brain that occurs."

Ethell explained that mutations in FMR1, a gene, have been known for more than a decade to cause FXS, but until now it has been unclear how these mutations cause unstable synapses and characteristic physical features of this disorder. The new findings expand on earlier work by the research group that showed that an MMP-9 inhibitor, minocycline, can reduce behavioral aspects of FXS, which then led to its use to treat FXS.

To further establish a causative role for MMP-9 in the development of FXS-associated features, including autistic behaviors, the authors generated mice that were missing both FMR1 and MMP-9. They found that while mice with a single FMR1 mutation showed autistic behaviors and macroorchidism (abnormally large testes), mice that also lacked MMP-9 showed no autistic behaviors.

"Our work points directly to MMP-9 over-activation as a cause for synaptic irregularities in FXS, with potential implications for other autistic spectrum disorders and perhaps Alzheimer's disease," said Doug Ethell, the head of Molecular Neurobiology at the Western University of Health Sciences, Pomona, Calif., and a coauthor on the study.

The research paper represents many years of bench work and effort by a dedicated team led by the Ethells. The work was primarily done in mice, but human tissue samples were also analyzed, with findings found to be consistent. Specifically, the work involved assessing behaviors, biochemistry, activity and anatomy of synaptic connections in the brain of a mouse model of FXS, as well as the creation of a new mouse line that lacked both the FXS gene and MMP-9.

FXS affects both males and females, with females often having milder symptoms than males. It is estimated that about 1 in 5,000 males are born with the disorder.

The Ethells were joined in the study by UCR's Harpreet Sidhu (first author of the research
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Contact: Iqbal Pittalwala
iqbal@ucr.edu
951-827-6050
University of California - Riverside
Source:Eurekalert  

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