| RNA-mediated neurodegeneration caused by the fragile X premutation rCGG repeats in Drosophila. | |
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MedLine Citation:
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PMID: 12948442 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Peng Jin; Daniela C Zarnescu; Fuping Zhang; Christopher E Pearson; John C Lucchesi; Kevin Moses; Stephen T Warren |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Neuron Volume: 39 ISSN: 0896-6273 ISO Abbreviation: Neuron Publication Date: 2003 Aug |
Date Detail:
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Created Date: 2003-09-01 Completed Date: 2003-11-10 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8809320 Medline TA: Neuron Country: United States |
Other Details:
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Languages: eng Pagination: 739-47 Citation Subset: IM |
Affiliation:
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Department of Human Genetics, Emory University, Atlanta, GA 30322, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Disease Models, Animal Drosophila Eye / pathology Female Fluorescent Antibody Technique Fragile X Mental Retardation Protein Fragile X Syndrome / genetics HSP70 Heat-Shock Proteins / metabolism Humans Inclusion Bodies / metabolism, pathology Male Microscopy, Electron Mutation Nerve Degeneration / genetics* Nerve Tissue Proteins / genetics* Neurons / metabolism, pathology*, ultrastructure RNA, Messenger / analysis, genetics* RNA-Binding Proteins* Reverse Transcriptase Polymerase Chain Reaction Transgenes Trinucleotide Repeat Expansion / genetics* Ubiquitin / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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P01 HD35576/HD/NICHD NIH HHS; R21 NS43536/NS/NINDS NIH HHS; R37 HD20521/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/FMR1 protein, human; 0/HSP70 Heat-Shock Proteins; 0/Nerve Tissue Proteins; 0/RNA, Messenger; 0/RNA-Binding Proteins; 0/Ubiquitin; 139135-51-6/Fragile X Mental Retardation Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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