Microarray analysis reveals induction of heat shock proteins mRNAs by the torsion dystonia protein, TorsinA.
An in-frame deletion (Delta E302/303) in the TorsinA gene has been demonstrated to be responsible for primary torsion dystonia, showing dominant inheritance with reduced penetrance. The Delta E302/303 torsinA mutation forms intracellular ER derived inclusions in a variety of cultured cells, which may suggest that the mutations might evoke ER stress. We used microarray analysis of human derived cell lines expressing the Delta E302/303 torsinA mutation in order to reveal alterations in gene expression in the hope of identifying genetic modifying loci or novel markers for disease pathogenesis. We identified transcriptional changes in multiple members of the heat shock protein family of genes, confirmed by reverse transcription-polymerase chain reaction, which could be indicative of ER stress. However, both wild type and mutant torsinA were affected to a similar extent, suggesting that this is not related to either disease state or the formation of ER-derived inclusions.
Baptista
Melisa J
MJ
Laboratory of Neurogenetics, National Institute on Aging/National Institutes of Health, 9000 Rockville Pike, Building 10, Room 6C103, MSC1589, 9000 Rockville Pike, Bethesda, MD 20892, USA. baptista@mail.nih.gov
O'Farrell
Casey
C
Hardy
John
J
Cookson
Mark R
MR
D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D004422:Dystonia Musculorum Deformans / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D018869:Heat-Shock Response; D006801:Humans; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D018832:Molecular Chaperones; D016297:Mutagenesis, Site-Directed; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection
D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; C108175:TOR1A protein, human