Linked Life Data

18502140

Source:http://linkedlifedata.com/resource/pubmed/id/18502140

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-6-23
pubmed:abstractText
In the present study, we prepared a SCA3 animal model by generating transgenic mice expressing polyglutamine-expanded ataxin-3-Q79. Ataxin-3-Q79 was expressed in brain areas implicated in SCA3 neurodegeneration, including cerebellum, pontine nucleus and substantia nigra. Ataxin-3-Q79 transgenic mice displayed motor dysfunction with an onset age of 5-6 months, and neurological symptoms deteriorated in the following months. A prominent neuronal loss was not found in the cerebellum of 10 to 11-month-old ataxin-3-Q79 mice displaying pronounced ataxic symptoms, suggesting that instead of neuronal demise, ataxin-3-Q79 causes neuronal dysfunction of the cerebellum and resulting ataxia. To test the involvement of transcriptional dysregulation in ataxin-3-Q79-induced cerebellar malfunction, microarray analysis and real-time RT-PCR assays were performed to identify altered cerebellar mRNA expressions of ataxin-3-Q79 mice. Compared to non-transgenic mice or mice expressing wild-type ataxin-3-Q22, 10 to 11-month-old ataxin-3-Q79 mice exhibited downregulated mRNA expressions of proteins involved in glutamatergic neurotransmission, intracellular calcium signaling/mobilization or MAP kinase pathways, GABA(A/B) receptor subunits, heat shock proteins and transcription factor regulating neuronal survival and differentiation. Upregulated expressions of Bax, cyclin D1 and CDK5-p39, which may mediate neuronal death, were also observed in ataxin-3-Q79 transgenic mice. The involvement of transcriptional abnormality in initiating the pathological process of SCA3 was indicated by the finding that 4 to 5-month-old ataxin-3-Q79 mice, which did not display neurological phenotype, exhibited downregulated mRNA levels of genes involved in glutamatergic signaling and signal transduction. Our study suggests that polyglutamine-expanded ataxin-3 causes cerebellar dysfunction and ataxia by disrupting the normal pattern of gene transcriptions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1095-953X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
89-101
pubmed:meshHeading
pubmed-meshheading:18502140-Animals, pubmed-meshheading:18502140-Blotting, Southern, pubmed-meshheading:18502140-Blotting, Western, pubmed-meshheading:18502140-Cerebellum, pubmed-meshheading:18502140-Disease Models, Animal, pubmed-meshheading:18502140-Gene Expression, pubmed-meshheading:18502140-Humans, pubmed-meshheading:18502140-Immunohistochemistry, pubmed-meshheading:18502140-Machado-Joseph Disease, pubmed-meshheading:18502140-Mice, pubmed-meshheading:18502140-Mice, Transgenic, pubmed-meshheading:18502140-Nuclear Proteins, pubmed-meshheading:18502140-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:18502140-Peptides, pubmed-meshheading:18502140-RNA, Messenger, pubmed-meshheading:18502140-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18502140-Transcription, Genetic, pubmed-meshheading:18502140-Transcription Factors, pubmed-meshheading:18502140-Trinucleotide Repeat Expansion
pubmed:year
2008
pubmed:articleTitle
Polyglutamine-expanded ataxin-3 causes cerebellar dysfunction of SCA3 transgenic mice 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