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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.
Behavioural Brain Research
|September 13, 2015
Summary
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.
