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Behav Brain Res. 2017 Jan 15;317:536-541. doi: 10.1016/j.bbr.2016.10.028. Epub 2016 Oct 18.

Sensorimotor tests unmask a phenotype in the DYT1 knock-in mouse model of dystonia.

Author information

1
Institute of Pharmacology, Pharmacy and Toxicology, Department of Veterinary Medicine, Leipzig University, An den Tierkliniken 15, 04103, Leipzig, Germany. Electronic address: franziska.richter@vmf.uni-leipzig.de.
2
Institute of Pharmacology, Pharmacy and Toxicology, Department of Veterinary Medicine, Leipzig University, An den Tierkliniken 15, 04103, Leipzig, Germany. Electronic address: julia.gerstenberger@vetmed.uni-leipzig.de.
3
Institute of Pharmacology, Pharmacy and Toxicology, Department of Veterinary Medicine, Leipzig University, An den Tierkliniken 15, 04103, Leipzig, Germany. Electronic address: anne.bauer@vetmed.uni-leipzig.de.
4
Department of Neurology and Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: chunchi@med.umich.edu.
5
Institute of Pharmacology, Pharmacy and Toxicology, Department of Veterinary Medicine, Leipzig University, An den Tierkliniken 15, 04103, Leipzig, Germany. Electronic address: angelika.richter@vetmed.uni-leipzig.de.

Abstract

Hereditary generalized dystonia is often caused by a GAG deletion in TOR1A (DYT1) that encodes for the protein torsinA. Although mutation carriers show alterations in neuronal connectivity and sensorimotor deficits, only 30% develop dystonia. Uncovering the factors triggering the dystonic symptoms and underlying pathophysiology would greatly benefit the development of more effective therapies. In DYT1 knock-in (KI) mice, the expression of torsinA mutant alters the connectivity of neurons and the function of striatal cholinergic interneurons. We aimed to determine if heterozygous DYT1 KI mice exhibit deficits in behavioural tests that explore the connectivity of the sensory and motor system. DYT1 KI mice were tested in cognitive tests and challenging motor paradigms, followed by the adhesive removal test and the adaptive rotating beam test which both require sensorimotor integration. DYT1 KI mice did not exhibit cognitive deficits and were able to perform similarly to wild type mice even in challenging motor tests with relatively stable sensory input. Conversely, DYT1 KI mice spent more time on sensing and removing an adhesive sticker from the back of the nose; they exhibited difficulty to traverse rotating rods, especially if the surface was smooth and the diameter small. Our observations further support a role of sensorimotor integration in manifestation of this movement disorder. Future studies in DYT1 KI mice will explore the involved neurocircuitry and underlying molecular mechanisms.

KEYWORDS:

Endophenotype; Genetic model; Sensorimotor impairments; Torsion dystonia

PMID:
27769743
DOI:
10.1016/j.bbr.2016.10.028
[Indexed for MEDLINE]

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