Title

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

Publication Date

2015

Journal Title

Neurobiology of Disease

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. (C) 2015 Elsevier Inc All rights reserved.

Volume Number

73

Pages

399-406

Document Type

Article

EPub Date

2014/12/03

Status

Faculty; Northwell Researcher

Facility

School of Medicine; Northwell Health

Primary Department

Molecular Medicine

Additional Departments

Neurology

PMID

25447231

DOI

10.1016/j.nbd.2014.10.020