Linked Life Data

14985428

Source:http://linkedlifedata.com/resource/pubmed/id/14985428

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2004-2-26
pubmed:abstractText
Nine neurodegenerative diseases including Huntington's disease (HD) and spinocerebellar ataxia type 7 (SCA7) are caused by an expansion of a polyglutamine (polyQ) stretch in the respective proteins. Aggregation of expanded polyQ-containing proteins into the nucleus is a hallmark of these diseases. Recent evidence indicates that transcriptional dysregulation may contribute to the molecular pathogenesis of these diseases. Using SCA7 and HD mouse models in which we recently described a retinal phenotype, we investigated whether altered gene expression underlies photoreceptor dysfunction. In both models, rhodopsin promoter activity was early and dramatically repressed, suggesting that downregulation of photoreceptor-specific genes plays a major role in polyQ-induced retinal dysfunction. Because the rhodopsin promoter drives mutant ataxin-7 expression in our SCA7 mice, we also assessed whether downregulation of mutant SCA7 transgene would reverse retinopathy progression and aggregate formation. Although residual expression of mutant ataxin-7 was found negligible from 9 weeks of age, SCA7 transgenic mice showed a progressive decline of photoreceptor activity leading to a complete loss of electroretinographic responses from 1 year of age. At this age, aggregates were cleared in only half of the photoreceptors, indicating that their formation is not fully reversible in this model. We demonstrate here that abolishing full-length mutant ataxin-7 expression did not reverse retinopathy progression in SCA7 mice, raising the possibility that some polyQ-induced pathological events might be irreversible.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
25
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1881-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14985428-Age Factors, pubmed-meshheading:14985428-Animals, pubmed-meshheading:14985428-Disease Models, Animal, pubmed-meshheading:14985428-Disease Progression, pubmed-meshheading:14985428-Down-Regulation, pubmed-meshheading:14985428-Electroretinography, pubmed-meshheading:14985428-Gene Expression Regulation, Developmental, pubmed-meshheading:14985428-Huntington Disease, pubmed-meshheading:14985428-Macromolecular Substances, pubmed-meshheading:14985428-Mice, pubmed-meshheading:14985428-Mice, Transgenic, pubmed-meshheading:14985428-Nerve Tissue Proteins, pubmed-meshheading:14985428-Nuclear Proteins, pubmed-meshheading:14985428-Peptides, pubmed-meshheading:14985428-Photoreceptor Cells, Vertebrate, pubmed-meshheading:14985428-Promoter Regions, Genetic, pubmed-meshheading:14985428-Recombinant Proteins, pubmed-meshheading:14985428-Retinal Degeneration, pubmed-meshheading:14985428-Rhodopsin, pubmed-meshheading:14985428-Spinocerebellar Ataxias, pubmed-meshheading:14985428-Transgenes, pubmed-meshheading:14985428-Trinucleotide Repeat Expansion
pubmed:year
2004
pubmed:articleTitle
Disease progression despite early loss of polyglutamine protein expression in SCA7 mouse model.
pubmed:affiliation
Department of Molecular Pathology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Médicale-Université Louis Pasteur, Illkirch, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't