Project Detail
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Office of Autism Research Coordination (OARC) logo

Elucidation and rescue of amygdala abnormalities in the Fmr1 mutant mouse model of fragile X syndrome  

Although the underlying causes of autism spectrum disorders (ASD) are complex, two aspects have emerged from studies over the years: 1) there is a large genetic component to ASD, and 2) ASD is a disorder of brain development. Converging lines of evidence support the hypothesis that mutations in genes that regulate synapse formation and function underlie ASD. One of the best current models for understanding the brain abnormalities in ASD is Fragile X Syndrome (FXS). FXS is a single gene neurodevelopmental disorder that results from an absence of expression of the mRNA binding protein-encoding Fmr1 gene. FXS is characterized by cognitive impairment and impaired social interaction. The latter takes the form of social avoidance/anxiety and/or autistic behavior, which leads to an approximately 45% prevalence of DSM-IV diagnosis of ASD in boys with FXS, thus making FXS the leading known genetic cause of autism. Therefore, although most cases of ASD likely involve interactions between multiple genetic pathways, the behavioral similarities and involvement of overlapping brain regions indicates that the study of FXS at the experimental or clinical level will contribute significantly to understanding the developmental alterations that occur in autism. The proposed research is directed toward the study of synaptic alterations in inhibitory transmission in the amygdala in the Fmr1 mutant animal model of FXS with two goals: 1) determination of the mechanism of altered inhibitory neurotransmission and 2) correction of these defects. This will be accomplished by a multidisciplinary approach combining electrophysiology, immunohistochemistry, neuroanatomy, mouse genetics and pharmacology. As approximately 45% in boys with FXS are autistic, the study of FXS and animal models of FXS is one of the best current approaches for understanding the biological underpinnings of autism. Project Status


Funder Autism Speaks
Fiscal Year Funding $150,000.00
Current Award Period 2010-2013
Project Number 5865
Principal Investigator Corbin, Joshua
Received ARRA Funding? No
Strategic Plan Question Question 2: How Can I Understand What Is Happening? (Biology)
Subcategory Molecular Pathways
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 2SD. Launch three studies that target improved understanding of the underlying biological pathways of genetic conditions related to autism (e.g. Fragile X, Rett syndrome, tuberous sclerosis complex) and how these conditions inform risk assessment and individualized intervention by 2012. IACC Recommended Budget: $9,000,000 over 5 years.
Federal or Private? Private
Institution George Washington University
State/Country District of Columbia
Web Link 1 Elucidation and rescue of amygdala abnormalities in the Fmr1 mutant mouse model of fragile X syndrome (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
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