title: Gait analysis in a mouse model resembling Leigh disease.
abstract: Leigh disease (LD) is one of the clinical phenotypes of mitochondrial OXPHOS disorders and also known as sub-acute necrotizing encephalomyelopathy. The disease has an incidence of 1 in 77,000 live births. Symptoms typically begin early in life and prognosis for LD patients is poor. Currently, no clinically effective treatments are available. Suitable animal and cellular models are necessary for the understanding of the neuropathology and the development of successful new therapeutic strategies. In this study we used the Ndufs4 knockout (Ndufs4(-/-)) mouse, a model of mitochondrial complex I deficiency. Ndusf4(-/-) mice exhibit progressive neurodegeneration, which closely resemble the human LD phenotype. When dissecting behavioral abnormalities in animal models it is of great importance to apply translational tools that are clinically relevant. To distinguish gait abnormalities in patients, simple walking tests can be assessed, but in animals this is not easy. This study is the first to demonstrate automated CatWalk gait analysis in the Ndufs4(-/-) mouse model. Marked differences were noted between Ndufs4(-/-) and control mice in dynamic, static, coordination and support parameters. Variation of walking speed was significantly increased in Ndufs4(-/-) mice, suggesting hampered and uncoordinated gait. Furthermore, decreased regularity index, increased base of support and changes in support were noted in the Ndufs4(-/-) mice. Here, we report the ability of the CatWalk system to sensitively assess gait abnormalities in Ndufs4(-/-) mice. This objective gait analysis can be of great value for intervention and drug efficacy studies in animal models for mitochondrial disease.
authors.affiliation: Nijmegen Center for Mitochondrial Disorders, Department of Paediatrics, Radboud UMC, Nijmegen, The Netherlands; Nijmegen Center for Mitochondrial Disorders, Department of Pharmacology and Toxicology, Radboud UMC, Nijmegen, The Netherlands. Electronic address: Ria.deHaas@radboudumc.nl.
authors.forename: Ria
authors.initials: R
authors.lastname: de Haas
authors.affiliation: Nijmegen Center for Mitochondrial Disorders, Department of Pharmacology and Toxicology, Radboud UMC, Nijmegen, The Netherlands.
authors.forename: Frans G
authors.initials: FG
authors.lastname: Russel
authors.affiliation: Nijmegen Center for Mitochondrial Disorders, Department of Paediatrics, Radboud UMC, Nijmegen, The Netherlands.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Smeitink
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001696:Biomechanical Phenomena; D004195:Disease Models, Animal; D042967:Electron Transport Complex I; D005684:Gait / Q000502:physiology*; D007794:Lameness, Animal / Q000209:etiology / Q000503:physiopathology*; D007888:Leigh Disease / Q000150:complications / Q000503:physiopathology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: C534449:Ndufs4 protein, mouse; D042967:Electron Transport Complex I
keywords: CatWalk system; Gait analysis; Mitochondrial complex I deficiency; Ndufs4 knockout mice