title: Sensorimotor tests unmask a phenotype in the DYT1 knock-in mouse model of dystonia.
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.
authors: 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.
authors: Franziska
authors: F
authors: Richter
authors: 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.
authors: Julia
authors: J
authors: Gerstenberger
authors: 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.
authors: Anne
authors: A
authors: Bauer
authors: 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.
authors: Chun-Chi
authors: CC
authors: Liang
authors: 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.
authors: Angelika
authors: A
authors: Richter
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D004195:Disease Models, Animal; D004421:Dystonia / Q000235:genetics* / Q000503:physiopathology*; D004422:Dystonia Musculorum Deformans / Q000235:genetics / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009069:Movement Disorders / Q000209:etiology; D009154:Mutation / Q000235:genetics*; D009425:Nesting Behavior / Q000502:physiology; D010641:Phenotype; D011596:Psychomotor Disorders / Q000209:etiology / Q000235:genetics
keywords: Endophenotype; Genetic model; Sensorimotor impairments; Torsion dystonia