Reference Report

Reference
Citation	Jin, P., Zarnescu, D.C., Zhang, F., Pearson, C.E., Lucchesi, J.C., Moses, K., Warren, S.T. (2003). RNA-mediated neurodegeneration caused by the Fragile X premutation rCGG repeats in Drosophila. Neuron 39(5): 739--747. (Export to RIS)
FlyBase ID	FBrf0162265
Publication Type	Research paper
PubMed ID	12948442
PubMed Abstract	Fragile X syndrome carriers have FMR1 alleles, called premutations, with an intermediate number of 5' untranslated CGG repeats between patients (>200 repeats) and normal individuals (<60 repeats). A novel neurodegenerative disease has recently been appreciated in some premutation carriers. As no neurodegeneration is seen in fragile X patients, who do not express FMR1, we hypothesize that lengthened rCGG repeats of the premutation transcript may lead to neurodegeneration. Here, using Drosophila melanogaster, we show that 90 rCGG repeats alone are sufficient to cause neurodegeneration. This phenotype is neuron specific and rCGG repeat dosage sensitive. Although devoid of mutant protein, this neurodegeneration exhibits neuronal inclusion bodies that are Hsp70 and ubiquitin positive. Overexpression of Hsp70 could suppress the neurodegeneration. These results demonstrate that neurodegenerative phenotype associated with fragile X premutation is indeed caused by the lengthened rCGG repeats and provide the first in vivo experimental demonstration of RNA-mediated neurodegeneration.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Neuron
Title	Neuron
Publication Year	1988-
ISBN/ISSN	0896-6273
Data from Reference
Alleles (10)
	Avic\GFP^{E.Scer\UAS.cJa} Hsc70-4^{K71S.Scer\UAS} Hsc70-4^Scer\UAS.cEa Scer\GAL4^Act5C.PI Scer\GAL4^dpp.blk1 Scer\GAL4^elav-C155 Scer\GAL4^GMR.PF T:Avic\GFP^EGFP Zzzz\CGG^{60.Scer\UAS.T:Avic\GFP-EGFP} Zzzz\CGG^{90.Scer\UAS.T:Avic\GFP-EGFP}
Constructs (8)
	P{Act5C-GAL4} P{GAL4-dpp.blk1} P{GAL4-ninaE.GMR} P{UAS-CGG60-EGFP} P{UAS-CGG90-EGFP} P{UAS-EGFP.J} P{UAS-Hsc70-4.K71S} P{UAS-Hsc70-4.WT}
Genes (10)
	Avic\GFP Hsc70-4 Hsp70Aa Hsp70Ab Hsp70Ba Hsp70Bb Hsp70Bbb Hsp70Bc Scer\GAL4 Zzzz\CGG
Insertions (1)
	P{GawB}elav^C155