title: TorsinA, the gene linked to early-onset dystonia, is upregulated by the dopaminergic toxin MPTP in mice.
abstract: Early-onset torsion dystonias are caused by a mutation in TorsinA, a protein widely expressed in the nervous system. Here we report the cloning of the murine TorsinA cDNA and a mRNA in situ hybridization analysis of the expression patterns of TorsinA over developmental periods relevant to the etiology of early-onset dystonias. Several studies have demonstrated a functional involvement of the nigrostriatal dopaminergic system in pathological mechanisms underlying dystonia. In this study, we show that the expression of TorsinA is significantly increased in the brain within hours of treatment with the dopaminergic toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice, suggesting that the TorsinA gene is regulated by cellular stress. These results provide insights into the pathophysiology of early-onset dystonia and strengthen links between the dopaminergic system and dystonia.
authors.affiliation: Pharmacology Institute, University of Heidelberg, Im Neunheimer Feld 366, 69120 Heidelberg, Germany. rohini.kuner@urz.uni-heidelberg.de
authors.forename: Rohini
authors.initials: R
authors.lastname: Kuner
authors.forename: Peter
authors.initials: P
authors.lastname: Teismann
authors.forename: Annette
authors.initials: A
authors.lastname: Trutzel
authors.forename: Jomana
authors.initials: J
authors.lastname: Naim
authors.forename: Angelika
authors.initials: A
authors.lastname: Richter
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmidt
authors.forename: Alfred
authors.initials: A
authors.lastname: Bach
authors.forename: Boris
authors.initials: B
authors.lastname: Ferger
authors.forename: Armin
authors.initials: A
authors.lastname: Schneider
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D017668:Age of Onset; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics*; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D004298:Dopamine / Q000378:metabolism*; D004422:Dystonia Musculorum Deformans / Q000235:genetics*; D020267:MPTP Poisoning / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; C491548:Dyt1 protein, mouse; D018832:Molecular Chaperones; D009498:Neurotoxins; D012333:RNA, Messenger; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine