Gait analysis in a mouse model resembling Leigh disease
| Autor: | Jan A.M. Smeitink, Ria de Haas, Frans G. M. Russel |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Mice 129 Strain Mitochondrial disease Lameness Animal Neuropathology Disease Biology Bioinformatics 03 medical and health sciences Behavioral Neuroscience Mice 0302 clinical medicine medicine Animals Leigh disease Gait Mice Knockout Electron Transport Complex I Behavior Animal NDUFS4 Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] medicine.disease Biomechanical Phenomena Preferred walking speed Mice Inbred C57BL Disease Models Animal 030104 developmental biology Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] Gait analysis Leigh Disease 030217 neurology & neurosurgery |
| Zdroj: | Behavioural Brain Research, 296, pp. 191-8 Behavioural Brain Research, 296, 191-8 |
| ISSN: | 0166-4328 |
| Popis: | Contains fulltext : 170843.pdf (Publisher’s version ) (Closed access) 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. |
| Databáze: | OpenAIRE |
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