| Characterization of the porcine TOR1A gene: The first step towards generation of a pig model for dystonia. | |
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MedLine Citation:
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PMID: 19028553 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The TOR1A (also named DYT1) gene encodes a protein, TorsinA, a member of the AAA+ superfamily of ATPases. The AAA+ proteins have diverse functions such as organelle biogenesis, proteosome function, chaperone function, membrane trafficking and microtubule regulation. However, the molecular function of TorsinA is still largely unknown. Mutations in the TOR1A gene, primarily a 3-bp (GAG) deletion are associated with early-onset autosomal dominant torsion dystonia. Animal models may help to provide information about the underlying cellular and molecular mechanism of early-onset generalized dystonia. The close anatomical, physiological, genetic and biochemical resemblance between man and pig suggest that this animal may constitute an excellent model for this disease. This work reports the cloning and analysis of the porcine (Sus scrofa) homologue of TOR1A. Two porcine TOR1A cDNAs were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), using oligonucleotide primers derived from in silico sequences. The porcine TOR1A cDNAs both encode a protein of 333 amino acids which shows a very high similarity to human (92%) TorsinA. Protein structure comparison of human and porcine TorsinA sequences revealed that there were few differences in the amino acid sequences between the two species and these are not likely to alter TorsinA structure and function. Quantitative real-time RT-PCR detection exhibited TOR1A mRNA expression in all analyzed porcine tissues, although at different levels. The TOR1A gene was demonstrated to be localized on porcine chromosome 1. Single nucleotide polymorphism (SNP) analysis revealed several SNPs in the porcine TOR1A gene, both in the coding region and also in the 3' UTR region. Overexpression of mutant (DeltaE303-304) porcine TorsinA in neuroblastoma cells leads to a more perinuclear localization compared with a cytoplasmatic localization for wildtype TorsinA. Furthermore, inclusion-like structures were observed. In conclusion, the results obtained for porcine TOR1A suggest that the pig could be an ideal model for early-onset generalized dystonia. |
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Authors:
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Carina Henriksen; Lone Bruhn Madsen; Christian Bendixen; Knud Larsen |
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Publication Detail:
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Type: Journal Article Date: 2008-11-06 |
Journal Detail:
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Title: Gene Volume: 430 ISSN: 1879-0038 ISO Abbreviation: Gene Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-01-05 Completed Date: 2009-02-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7706761 Medline TA: Gene Country: Netherlands |
Other Details:
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Languages: eng Pagination: 105-15 Citation Subset: IM |
Affiliation:
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Department of Genetics and Biotechnology, Faculty of Agricultural Sciences, University of Aarhus, Blichers Alle 20, P.O. Box 50, DK-8830 Tjele, Denmark. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/EF101283; EF101284; EU616811; EU702752 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Base Sequence Blotting, Western Cell Line DNA, Complementary / genetics Disease Models, Animal Dystonia / genetics* Gene Expression Profiling Gene Expression Regulation Genome / genetics Humans Molecular Chaperones / chemistry, genetics*, metabolism Molecular Sequence Data Mutant Proteins / chemistry, genetics, metabolism Polymorphism, Single Nucleotide / genetics Protein Transport RNA, Messenger / genetics, metabolism Radiation Hybrid Mapping Rats Subcellular Fractions / metabolism Sus scrofa / genetics* |
| Chemical | |
Reg. No./Substance:
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0/DNA, Complementary; 0/Molecular Chaperones; 0/Mutant Proteins; 0/RNA, Messenger |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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