Fragile X syndrome target analysis and its contribution to autism

  • Awarded: 2012
  • Award Type: Research
  • Award #: 240233

Autism spectrum disorders and fragile X syndrome have a remarkable clinical association and share biological ties to the molecular pathways critical for communication between brain cells, at synaptic junctions. Although a large number of genes have been implicated in autism, fragile X syndrome is caused by the loss of a single gene that encodes FMRP, a protein that regulates many messenger RNAs (mRNAs) before they are expressed as proteins.

Thomas Tuschl and his colleagues at The Rockefeller University in New York have identified a substantial number of FMRP target mRNAs that are independently associated with autism, indicating that these could be critical players in the etiology of both disorders. Tuschl’s lab, which specializes in RNA and systems biology, aims to characterize the regulatory impact of FMRP on its targets to identify potential therapeutic targets for treating autism and fragile X syndrome. The researchers also hope to identify other regulatory factors that work together with, or independently of, FMRP to uncover additional strategies for manipulating these targets.

The loss of FMRP affects multiple tissues and organ systems, particularly the brain and gonads. The Tuschl laboratory plans to use mice lacking FMRP to assess how FMRP targets are deregulated across tissues, by visualizing its targets at both the mRNA and protein levels. They also plan to extend these studies to human tissues from the Simons Simplex Collection, a database of families that include one child with autism and unaffected parents and siblings, analyzing these targets as potential diagnostic biomarkers for autism spectrum disorders.

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