title: 18FDG-microPET and MR DTI findings in Tor1a+/- heterozygous knock-out mice.
abstract: TorsinA is an important protein in brain development, and plays a role in the regulation of neurite outgrowth and synaptic function. Patients with the most common form of genetic dystonia carry a mutation (DYT1) in one copy of the Tor1a gene, a 3-bp deletion, causing removal of a single glutamic acid from torsinA. Previous imaging studies have shown that abnormal cerebellar metabolism and damaged cerebello-thalamo-cortical pathway contribute to the pathophysiology of DYT1 dystonia. However, how a mutation in one copy of the Tor1a gene causes these abnormalities is not known. We studied Tor1a heterozygous knock-out mice in vivo with FDG-PET and ex vivo with diffusion tensor imaging. We found metabolic abnormalities in cerebellum, caudate-putamen, globus pallidus, sensorimotor cortex and subthalamic nucleus. We also found that FA was increased in caudate-putamen, sensorimotor cortex and brainstem. We compared our findings with a previous imaging study of the Tor1a knock-in mice. Our study suggested that having only one normal copy of Tor1a gene may be responsible for the metabolic abnormalities observed; having a copy of mutant Tor1a, on the other hand, may be responsible for white matter pathway damages seen in DYT1 dystonia subjects.
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, NY 11030, USA.
authors.forename: An
authors.initials: A
authors.lastname: Vo
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, NY 11030, USA.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sako
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, NY 11030, USA; Department of Molecular Medicine, Hofstra University, NY 11549, USA; Department of Psychiatry, New York University, NY 10012, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Dewey
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, NY 11030, USA.
authors.forename: David
authors.initials: D
authors.lastname: Eidelberg
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, NY 11030, USA; Department of Molecular Medicine, Hofstra University, NY 11549, USA; Department of Radiology, Albert Einstein College of Medicine, NY 10461, USA; Institute of Biomedical Engineering, Boğaziçi University, Istanbul, Turkey. Electronic address: aulug@nshs.edu.
authors.forename: Aziz M
authors.initials: AM
authors.lastname: Uluğ
mesh_terms: D000818:Animals; D056324:Diffusion Tensor Imaging / Q000379:methods*; D004421:Dystonia / Q000378:metabolism* / Q000473:pathology; D019788:Fluorodeoxyglucose F18; D066128:Gray Matter / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D066127:White Matter / Q000378:metabolism* / Q000473:pathology
chemical_list: C491548:Dyt1 protein, mouse; D018832:Molecular Chaperones; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: DTI; Dystonia; Glucose metabolism; Heterozygous knock-out mice; Tor1a; TorsinA