Research objectives and content
The fragile X syndrome is the most common form of inherited mental retardation in man and is caused by a dynamic mutation in the FMR-1 gene, that it is located in Xq27.3. The mutational basis of the syndrome is an expansion of a trinucleotide repeat (CGG) just upstream of coding region. As a result, transcription suppression through hypermethylation of the promoter region occurs. Lack of the expression of the gene product, FMRP, is responsible for the pathogenesis of the fragile X syndrome. Thus far the physiological funcion of FMRP is unknown. An understanding of the function of FMRP would provide insight into the molecular basis of the fragile X syndrome.The goal of this study is further characterization of FMRP in neurons using different experimental approaches.
Training content (objective, benefit and expected impact)
Using biotinylated antibodies against FMRP I will study the expression pattern of FMRP in normal and transgenic mice, with special emphasis to the central nervous system. At the subcellular level I will study the routing of FMRP, using cultured neurons which are transfected with a plasmid containing either wildtype or mutant forms of FMRP.In addition, biochemical studies will be performed to characterize tne different molecular forms and possible interaction(s) of FMRP with other proteins or RNA's. Links with industry / industrial relevance (22)