Linked Life Data

19909779

Source:http://linkedlifedata.com/resource/pubmed/id/19909779

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-2-22
pubmed:abstractText
In the present study, we prepared an animal model of adult-onset spinocerebellar ataxia type 7 (SCA7) by generating transgenic mice expressing polyglutamine-expanded ataxin-7-Q52. Mutant ataxin-7-Q52 was expressed in brain areas implicated in SCA7 neurodegeneration, including cerebellum and inferior olivary nucleus. Ataxin-7-Q52 transgenic mice exhibited symptoms of motor dysfunction with an onset age of 7 months, and neurological phenotypes deteriorated in the following months. Ten to eleven-month-old ataxin-7-Q52 mice displayed ataxic symptoms without prominent cerebellar neuronal death, suggesting that ataxin-7-Q52 causes cerebellar malfunction and ataxia. To investigate the involvement of transcriptional dysregulation in ataxin-7-Q52-induced cerebellar dysfunction, microarray analysis and real-time RT-PCR assays were performed to identify altered cerebellar mRNA expressions of 10-11-month-old ataxin-7-Q52 transgenic mice. Ataxin-7-Q52 mice exhibited downregulated mRNA expressions of proteins involved in glutamatergic transmission, signal transduction, myelin formation, deubiquitination, axon transport, neuronal differentiation or glial functions and heat shock proteins. The involvement of transcriptional abnormality in initiating SCA7 pathological process was indicated by the finding that 6-month-old ataxin-7-Q52 transgenic mice, which did not display noticeable ataxic symptoms, exhibited dysregulated mRNA expressions. Our study suggests that polyglutamine-expanded ataxin-7-induced transcriptional dysregulation causes cerebellar dysfunction and ataxia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1872-9754
pubmed:author
pubmed:copyrightInfo
Copyright 2009 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
329-39
pubmed:meshHeading
pubmed-meshheading:19909779-Animals, pubmed-meshheading:19909779-Behavior, Animal, pubmed-meshheading:19909779-Blotting, Western, pubmed-meshheading:19909779-Disease Models, Animal, pubmed-meshheading:19909779-Down-Regulation, pubmed-meshheading:19909779-Gene Expression Regulation, pubmed-meshheading:19909779-Immunohistochemistry, pubmed-meshheading:19909779-Mice, pubmed-meshheading:19909779-Mice, Transgenic, pubmed-meshheading:19909779-Microscopy, Electron, pubmed-meshheading:19909779-Nerve Tissue Proteins, pubmed-meshheading:19909779-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:19909779-Peptides, pubmed-meshheading:19909779-RNA, Messenger, pubmed-meshheading:19909779-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19909779-Spinocerebellar Ataxias, pubmed-meshheading:19909779-Transcription, Genetic
pubmed:year
2010
pubmed:articleTitle
Polyglutamine-expanded ataxin-7 causes cerebellar dysfunction by inducing transcriptional dysregulation.
pubmed:affiliation
Department of Anesthesiology, Chang Gung Memorial Hospital, Kwei-San, Tao-Yuan, Taiwan, ROC.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't