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Neurobiol Dis. 2015 Jan;73:399-406. doi: 10.1016/j.nbd.2014.10.020. Epub 2014 Nov 4.

18FDG-microPET and MR DTI findings in Tor1a+/- heterozygous knock-out mice.

Author information

1
Center for Neurosciences, The Feinstein Institute for Medical Research, NY 11030, USA.
2
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.
3
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.

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.

KEYWORDS:

DTI; Dystonia; Glucose metabolism; Heterozygous knock-out mice; Tor1a; TorsinA

PMID:
25447231
DOI:
10.1016/j.nbd.2014.10.020
[Indexed for MEDLINE]

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