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Treating autistic-like traits in mouse models of Fragile X Syndrome

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United States

Fragile X syndrome (FXS) is the most common known genetic cause of autism. Human genetic studies have revealed that fragile X syndrome (FXS) is caused by a mutation in a single gene that prevents expression of a single protein. Brain developmental in the absence of this single protein is associated with significant morbidity including impaired cognitive function, attention deficit and hyperactivity, anxiety, obsessive-compulsive and autistic behaviors. Therefore, knowledge of the function of this protein as well as therapeutic targets may potentially be helpful to discoveries in autism research. The Paylor lab has recently demonstrated that specific strains of fragile X mice display ‘autistic-like' traits including abnormalities in social interaction, compulsive behaviors and anxiety-related responses. Recent studies indicate that compounds which target the glutamate receptor can also effectively treat abnormalities in brain cell function, seizures and some abnormal behaviors in these fragile X mice. Therefore, the aim of these is to assess efficacy of mGluR5 antagonists in this animal model of autism. Significance: This proposed collaborative research program offers a unique opportunity to evaluate the impact of novel potential therapeutic agents not only in mouse models of FXS, but also mouse models of FXS that display unique autistic-like features.