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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2001-10-2
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pubmed:abstractText |
Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disorder caused by a CAG repeat expansion. To determine the mechanism of neurotoxicity, we produced transgenic mice and observed a cone-rod dystrophy. Nuclear inclusions were present, suggesting that the disease pathway involves the nucleus. When yeast two-hybrid assays indicated that cone-rod homeobox protein (CRX) interacts with ataxin-7, we performed further studies to assess this interaction. We found that ataxin-7 and CRX colocalize and coimmunoprecipitate. We observed that polyglutamine-expanded ataxin-7 can dramatically suppress CRX transactivation. In SCA7 transgenic mice, electrophoretic mobility shift assays indicated reduced CRX binding activity, while RT-PCR analysis detected reductions in CRX-regulated genes. Our results suggest that CRX transcription interference accounts for the retinal degeneration in SCA7 and thus may provide an explanation for how cell-type specificity is achieved in this polyglutamine repeat disease.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Eye Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Prions,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/ataxin-7,
http://linkedlifedata.com/resource/pubmed/chemical/cone rod homeobox protein,
http://linkedlifedata.com/resource/pubmed/chemical/polyglutamine
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0896-6273
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pubmed:author |
pubmed-author:ChenSS,
pubmed-author:EinumD DDD,
pubmed-author:FuY HYH,
pubmed-author:HuangJJ,
pubmed-author:HurleyJ BJB,
pubmed-author:KoszdinK LKL,
pubmed-author:La SpadaA RAR,
pubmed-author:LiL YLY,
pubmed-author:LibbyR TRT,
pubmed-author:MartinezR ARA,
pubmed-author:PossinD EDE,
pubmed-author:PtácekL JLJ,
pubmed-author:SmithA CAC,
pubmed-author:SopherB LBL,
pubmed-author:TreutingP MPM,
pubmed-author:WangXX,
pubmed-author:WareC BCB
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pubmed:issnType |
Print
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pubmed:day |
27
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pubmed:volume |
31
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
913-27
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11580893-Age Factors,
pubmed-meshheading:11580893-Animals,
pubmed-meshheading:11580893-Cell Line,
pubmed-meshheading:11580893-Cell Nucleus,
pubmed-meshheading:11580893-Disease Models, Animal,
pubmed-meshheading:11580893-Electroretinography,
pubmed-meshheading:11580893-Eye Proteins,
pubmed-meshheading:11580893-Gene Expression Profiling,
pubmed-meshheading:11580893-Genes, Synthetic,
pubmed-meshheading:11580893-Homeodomain Proteins,
pubmed-meshheading:11580893-Humans,
pubmed-meshheading:11580893-Macromolecular Substances,
pubmed-meshheading:11580893-Mice,
pubmed-meshheading:11580893-Mice, Transgenic,
pubmed-meshheading:11580893-Nerve Tissue Proteins,
pubmed-meshheading:11580893-Nuclear Proteins,
pubmed-meshheading:11580893-Peptides,
pubmed-meshheading:11580893-Photoreceptor Cells, Vertebrate,
pubmed-meshheading:11580893-Prions,
pubmed-meshheading:11580893-Promoter Regions, Genetic,
pubmed-meshheading:11580893-Protein Binding,
pubmed-meshheading:11580893-Retinal Degeneration,
pubmed-meshheading:11580893-Spinocerebellar Ataxias,
pubmed-meshheading:11580893-Synaptic Transmission,
pubmed-meshheading:11580893-Trans-Activators,
pubmed-meshheading:11580893-Transcriptional Activation,
pubmed-meshheading:11580893-Transfection,
pubmed-meshheading:11580893-Transgenes,
pubmed-meshheading:11580893-Trinucleotide Repeats,
pubmed-meshheading:11580893-Two-Hybrid System Techniques
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pubmed:year |
2001
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pubmed:articleTitle |
Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7.
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pubmed:affiliation |
Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA 98195, USA. laspada@u.washington.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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