Description) Fragile X syndrome is caused by a triplet nucleotide CGG expansion within the 5' untranslated region in the gene FMR1, resulting in the absence of the gene product, FMRP, a selective RNA-binding protein associated with ribosomes and enriched in nervous system. The compelling challenge in fragile X research is to understand the cellular pathogenesis by which the lack of FMRP gives rise to mental retardation and associated behavioral abnormalities. One potential approach is to assay the FMR1 within a simpler, well-characterized model organism. The investigators propose to uncover the synaptic defects of fragile X syndrome, and identify and characterize novel FMR1 interacting genes in Drosophila. They have identified a FMR1 gene homologue in Drosophila, dFXR, and hypothesized that the function of FMR1 is conserved between Drosophila and human. Taking advantage of powerful Drosophila genetics, they propose to systemically investigate the neurological functions of FMRP by a three-step approach.
Specific Aim 1 will generate a series of dFXR mutants, including """"""""loss of function"""""""" mutants by targeted knockout and """"""""gain of function"""""""" mutants by manipulating the expression of transgenes.
Specific Aim 2 will characterize the neurological functions of dFXR, focusing on synaptic development, function, and plasticity.
Specific Aim 3 will search for novel dFXR interacting genes with a genetic enhancer / suppressor screening and microarray technology. This application therefore complements and extends the parallel studies on mammalian systems.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD040654-06
Application #
6863636
Study Section
Special Emphasis Panel (ZHD1-MRG-C (15))
Program Officer
Oster-Granite, Mary Lou
Project Start
2001-04-20
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2007-03-31
Support Year
6
Fiscal Year
2005
Total Cost
$302,000
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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