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Author Notes:

Correspondence: H. A. Jinnah, M.D., Ph.D., 6300 Woodruff Memorial Research Building, Department of Neurology, Emory University, Atlanta GA, 30322; Phone: 404-727-9107; Email: hjinnah@emory.edu

Acknowledgments: We thank Dr. William Dauer for making the DYT1 knock-in mice available for these studies.

Thanks are also due to Susan Jenkins and Jean-Francois Pare for their technical help with the processing of tissue for electron microscopy studies.


Research Funding:

This work was supported in part by The Dystonia Medical Research Foundation, NIH grants NS040470 and NS033592, and the Yerkes Primate Centre base grant from NCRR (RR00165).


  • Mouse mutant
  • anatomy
  • Golgi histochemistry
  • stereology
  • striatum
  • electron microscopy

Subtle microstructural changes of the striatum in a DYT1 knock-in mouse model of dystonia


Journal Title:

Neurobiology of Disease


Volume 54


, Pages 362-371

Type of Work:

Article | Post-print: After Peer Review


The dystonias are comprised of a group of disorders that share common neurological abnormalities of involuntary twisting or repetitive movements and postures. The most common inherited primary dystonia is DYT1 dystonia, which is due to loss of a GAG codon in the TOR1A gene that encodes torsinA. Autopsy studies of brains from patients with DYT1 dystonia have revealed few abnormalities, although recent neuroimaging studies have implied the existence of microstructural defects that might not be detectable with traditional histopathological methods. The current studies took advantage of a knock-in mouse model for DYT1 dystonia to search for subtle anatomical abnormalities in the striatum, a region often implicated in studies of dystonia. Multiple abnormalities were identified using a combination of quantitative stereological measures of immunohistochemical stains for specific neuronal populations, morphometric studies of Golgi-stained neurons, and immuno-electron microscopy of synaptic connectivity. In keeping with other studies, there was no obvious loss of striatal neurons in the DYT1 mutant mice. However, interneurons immunoreactive for choline acetyltransferase or parvalbumin were larger in the mutants than in control mice. In contrast, interneurons immunoreactive for neuronal nitric oxide synthase were smaller in the mutants than in controls. Golgi histochemical studies of medium spiny projection neurons in the mutant mice revealed slightly fewer and thinner dendrites, and a corresponding loss of dendritic spines. Electron microscopic studies showed a reduction in the ratio of axo-spinous to axo-dendritic synaptic inputs from glutamatergic and dopaminergic sources in mutant mice compared with controls. These results suggest specific anatomical substrates for altered signaling in the striatum and potential correlates of the abnormalities implied by human imaging studies of DYT1 dystonia.

Copyright information:

© 2012 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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