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Updated: Jun 23, 2025
Measuring Progressive Neurological Disability in a Mouse Model of Multiple Sclerosis
Published on: November 14, 2016
Longitudinal quantitative assessment of TMEV-IDD-induced MS phenotypes in two inbred mouse strains using automated
Iskra Djabirska1, Laetitia Delaval1, Audrey Tromme1
1Department of Pathology, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liege, Liège 4000, Belgium; Prevor Research Laboratories, Valmondois 95760, France.
Abstract:
Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system affecting over 2.5 million people worldwide. Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is a murine model that reproduces the progressive form of MS and serves as a reference model for studying virus-induced demyelination. Certain mouse strains such as SJL are highly susceptible to this virus and serve as a prototype strain for studying TMEV infection. Other strains such as SWR are also susceptible, but their disease course following TMEV infection differs from SJL's. The quantification of motor and behavioral deficits following the induction of TMEV-IDD could help identify the differences between the two strains. Motor deficits have commonly been measured with the rotarod apparatus, but a multicomponent assessment tool has so far been lacking. For that purpose, we present a novel way of quantifying locomotor deficits, gait alterations and behavioral changes in this well-established mouse model of multiple sclerosis by employing automated video analysis technology (The PhenoTyper, Noldus Information Technology). We followed 12 SJL and 12 SWR female mice and their mock-infected counterparts over a period of 9 months following TMEV-IDD induction. We demonstrated that SJL and SWR mice both suffer significant gait alterations and reduced exploration following TMEV infection. However, SJL mice also display an earlier and more severe decline in spontaneous locomotion, especially in velocity, as well as in overall activity. Maintenance behaviors such as eating and grooming are not affected in either of the two strains. The system also showed differences in mock-infected mice from both strains, highlighting an age-related decline in spontaneous locomotion in the SJL strain, as opposed to hyperactivity in the SWR strain. Our study confirms that this automated video tracking system can reliably track the progression of TMEV-IDD for 9 months. We have also shown how this system can be utilized for longitudinal phenotyping in mice by describing useful parameters that quantify locomotion, gait and behavior.
Insights
We developed a novel automated video analysis system to track motor and behavioral changes in mice with Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), a model for multiple sclerosis (MS). The system reliably quantifies disease progression and strain-specific differences in locomotion and gait.
Area of Science:
- Neuroscience
- Immunology
- Animal Models
Background:
- Multiple sclerosis (MS) is a chronic central nervous system disease affecting millions globally.
- Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is a key murine model for studying MS.
- Quantifying motor and behavioral deficits in TMEV-IDD is crucial for understanding disease progression and strain differences.
Purpose of the Study:
- To introduce a novel automated video analysis system for quantifying locomotor, gait, and behavioral changes in TMEV-IDD.
- To compare disease progression in susceptible SJL and SWR mouse strains using this new system.
- To establish a reliable method for longitudinal phenotyping in TMEV-IDD mouse models.
Main Methods:
- Automated video analysis using The PhenoTyper (Noldus Information Technology) to track mice over 9 months.
- Induction of TMEV-IDD in SJL and SWR mouse strains and comparison with mock-infected controls.
- Quantification of parameters including spontaneous locomotion, velocity, gait alterations, exploration, and maintenance behaviors.
Main Results:
- Both SJL and SWR mice showed significant gait alterations and reduced exploration post-TMEV infection.
- SJL mice exhibited an earlier and more severe decline in spontaneous locomotion and activity compared to SWR mice.
- The system also identified age-related locomotion changes in mock-infected SJL and SWR mice, demonstrating its sensitivity.
Conclusions:
- Automated video analysis provides a reliable and sensitive method for tracking TMEV-IDD progression over 9 months.
- This technology effectively differentiates disease phenotypes between SJL and SWR mouse strains.
- The system offers valuable parameters for longitudinal phenotyping in mouse models of neurological diseases like MS.
