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Updated: Apr 4, 2026
Sagittal Plane Kinematic Gait Analysis in C57BL/6 Mice Subjected to MOG35-55 Induced Experimental Autoimmune Encephalomyelitis
Published on: November 4, 2017
Gait analysis in a mouse model resembling Leigh disease
Ria de Haas1, Frans G Russel2, Jan A Smeitink3
1Nijmegen 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.
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.
Insights
Leigh disease mouse models show gait abnormalities using automated CatWalk analysis. This objective method aids in developing treatments for this rare mitochondrial disorder.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Genetics
Background:
- Leigh disease (LD), a severe neurodegenerative disorder, stems from mitochondrial oxidative phosphorylation (OXPHOS) defects.
- Current treatments for LD are ineffective, necessitating robust animal models for research.
- The Ndufs4 knockout mouse model mimics human LD, displaying progressive neurodegeneration.
Purpose of the Study:
- To evaluate the utility of automated CatWalk gait analysis in the Ndufs4(-/-) mouse model of Leigh disease.
- To identify and quantify specific gait abnormalities indicative of neurodegeneration in this model.
Main Methods:
- Utilized the Ndufs4 knockout mouse model, a well-established model for mitochondrial complex I deficiency.
- Employed automated CatWalk gait analysis to objectively assess locomotion in Ndufs4(-/-) and control mice.
- Analyzed dynamic, static, coordination, and support parameters of gait.
Main Results:
- Ndufs4(-/-) mice exhibited significantly altered gait parameters compared to controls.
- Increased variation in walking speed indicated hampered and uncoordinated movement.
- Key findings included a decreased regularity index, increased base of support, and altered support parameters.
Conclusions:
- Automated CatWalk gait analysis is a sensitive and objective tool for detecting gait abnormalities in the Ndufs4(-/-) mouse model.
- This method can significantly aid in preclinical studies, including drug efficacy testing for Leigh disease.
- Objective gait analysis provides valuable insights for understanding LD neuropathology and developing therapeutic strategies.
