title: High-speed video gait analysis reveals early and characteristic locomotor phenotypes in mouse models of neurodegenerative movement disorders.
abstract: Neurodegenerative diseases of the central nervous system frequently affect the locomotor system resulting in impaired movement and gait. In this study we performed a whole-body high-speed video gait analysis in three different mouse lines of neurodegenerative movement disorders to investigate the motor phenotype. Based on precise computerized motion tracking of all relevant joints and the tail, a custom-developed algorithm generated individual and comprehensive locomotor profiles consisting of 164 spatial and temporal parameters. Gait changes observed in the three models corresponded closely to the classical clinical symptoms described in these disorders: Muscle atrophy due to motor neuron loss in SOD1 G93A transgenic mice led to gait characterized by changes in hind-limb movement and positioning. In contrast, locomotion in huntingtin N171-82Q mice modeling Huntington's disease with basal ganglia damage was defined by hyperkinetic limb movements and rigidity of the trunk. Harlequin mutant mice modeling cerebellar degeneration showed gait instability and extensive changes in limb positioning. Moreover, model specific gait parameters were identified and were shown to be more sensitive than conventional motor tests. Altogether, this technique provides new opportunities to decipher underlying disease mechanisms and test novel therapeutic approaches.
authors.affiliation: Institute for Regenerative Medicine-IREM, University of Zurich, 8952 Schlieren, Switzerland.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Preisig
authors.affiliation: Institute for Regenerative Medicine-IREM, University of Zurich, 8952 Schlieren, Switzerland.
authors.forename: Luka
authors.initials: L
authors.lastname: Kulic
authors.affiliation: Institute for Regenerative Medicine-IREM, University of Zurich, 8952 Schlieren, Switzerland.
authors.forename: Maik
authors.initials: M
authors.lastname: Krüger
authors.affiliation: Institute for Regenerative Medicine-IREM, University of Zurich, 8952 Schlieren, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Wirth
authors.affiliation: Institute for Regenerative Medicine-IREM, University of Zurich, 8952 Schlieren, Switzerland.
authors.forename: Jordan
authors.initials: J
authors.lastname: McAfoose
authors.affiliation: Institute for Regenerative Medicine-IREM, University of Zurich, 8952 Schlieren, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Späni
authors.affiliation: Institute for Regenerative Medicine-IREM, University of Zurich, 8952 Schlieren, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Gantenbein
authors.affiliation: Institute for Regenerative Medicine-IREM, University of Zurich, 8952 Schlieren, Switzerland.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Derungs
authors.affiliation: Institute for Regenerative Medicine-IREM, University of Zurich, 8952 Schlieren, Switzerland.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
authors.affiliation: Institute for Regenerative Medicine-IREM, University of Zurich, 8952 Schlieren, Switzerland. Electronic address: tobias.welt@bli.uzh.ch.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welt
mesh_terms: D000465:Algorithms; D000818:Animals; D001696:Biomechanical Phenomena; D004195:Disease Models, Animal; D018450:Disease Progression; D005684:Gait / Q000502:physiology; D006614:Hindlimb / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000503:physiopathology*; D010641:Phenotype; D045442:Rotarod Performance Test; D013997:Time Factors; D060726:Torso / Q000503:physiopathology; D014741:Video Recording / Q000379:methods
keywords: Amyotrophic lateral sclerosis; Cerebellar ataxia; Huntington's disease; Locomotion; Neurodegeneration; Video gait analysis