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Category CDBセミナー
Date and Time 2007-02-26 16:00 - 16:30
Venue Seminar Room A7F
Speaker Yong Q. Zhang
Affiliation Institute of Genetics and Developmental Biology, Chinese Academy of Sciences
Title Genetic approach to dissect the mechanisms of Fragile X mental retardation
Poster click here to download(PDF)
Host Fumio Matsuzaki
Summary Fragile X Syndrome (FXS) is the most common form of inheritable mental retardation resulted from the absence of the Fragile X Mental Retardation Protein (FMRP) encoded by FMR1. FMRP is an RNA binding protein, interacting with many other proteins to regulate the translation of its target mRNAs. However, most of its mRNA targets and interacting proteins remain uncharacterized, and the specificity by which FMRP interacts with its various partners is still elusive. Previous work on FMRP mainly took a reverse genetics approach. Now we are taking a forward genetics approach, performing extensive and large-scale genetic screens in Drosophila to isolate and characterize as many mutants as possible in the fly genome. The genetic screens including classical chemical mutagenesis, chromosomal deficiency screen, and EP overexpression screen are based on the lethality or rough eye phenotype caused by an overexpression of Drosophila homologue of FMRP, dFMRP. Previously identified dFMRP partners such as Futsch and Lgl (encoded by lethal (2) giant larvae) were pulled out from the screens, validating the screening schemes. A long list of mutants with mutations in dfmr1 itself and in dFMRP interacting genes is emerging. So far we have generated more than 100 dFMRP suppressors from the chemical mutagenesis alone; preliminary analyses of the first batch of mutants showed that 53 suppressors have mutations within dfmr1, while 24 mutants are intergenic dFMRP suppressors. The point mutations are located in different conserved domains of FMRP, providing invaluable reagents to elucidate the structural and functional relationship of FMRP. Intergenic dFMRP suppressors isolated from various screens are being mapped and characterized to unravel the molecular pathway in which FMRP participates. Due to the high structural and functional homology between Drosophila FMRP and human FMRP, our study with powerful forward genetics approach available in Drosophila will shed light on the roles of FMRP in the nervous system, which in turn will facilitate the development of a drug for the debilitating disease.
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