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Updated: Aug 7, 2026
Modeling Charcot-Marie-Tooth Disease In Vitro by Transfecting Mouse Primary Motoneurons
Published on: January 7, 2019
Cell death pathways differ in several mouse models with motoneurone disease: analysis of pure motoneurone populations
Florence E Perrin1, Gaelle Boisset, Aurélien Lathuilière
1Department of Basic Neuroscience, Faculty of Medicine, Geneva, Switzerland.
Abstract:
To identify candidate genes that are responsible for motoneurone degeneration, we combined laser capture microdissection with microarray technology. We analysed gene expression in pure motoneurones from two mouse mutants that develop motoneurone degeneration, progressive motor neuronopathy and wobbler. At a presymptomatic age, there was a significant differential expression of a restricted number of genes (25 and 72 in progressive motor neuronopathy and wobbler respectively, of 22 600 transcripts screened). We compared these results to our previous analyses in the copper-zinc superoxide dismutase mutant mouse (SOD1(G93A)) in which we observed a de-regulation of 27 genes. Some of these genes were de-regulated uniquely in one mouse mutant and some have already been identified in cell death pathways implicated in amyotrophic lateral sclerosis and animal models of motoneurone degeneration (i.e. de-regulation of intermediate filaments, axonal transport, the ubiquitin-proteasome system and excitotoxicity). One gene, vimentin, was differentially up-regulated in all mouse mutants; this main candidate gene has been confirmed by in situ hybridization and immunohistochemistry to be expressed in motoneurones in all mouse mutants. Furthermore, vimentin expression correlated with the state of motoneurone degeneration. These results identify early molecular changes that may be involved in the pathogenesis of motoneurones leading to cell death and favour a complex multipathway induction of the disease; surprisingly, there was no important modification in cell death-associated genes. This is the first study to show a clear difference in the genes that are de-regulated at an early stage in three different mouse models of motoneurone disease.
Insights
Researchers identified early gene expression changes in mouse models of motoneurone degeneration. Vimentin was consistently upregulated across models, suggesting its role in motor neuron disease pathogenesis.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Motoneurone degeneration underlies several debilitating neurological disorders.
- Identifying early molecular events is crucial for understanding disease pathogenesis.
- Existing models show de-regulation in pathways like axonal transport and excitotoxicity.
Purpose of the Study:
- To identify candidate genes involved in motoneurone degeneration.
- To compare gene expression profiles across different mouse models of motoneurone disease.
- To uncover early molecular changes preceding symptom onset.
Main Methods:
- Laser capture microdissection to isolate pure motoneurones.
- Microarray technology to analyze gene expression.
- In situ hybridization and immunohistochemistry to validate gene expression.
Main Results:
- Significant differential gene expression observed in presymptomatic mice (25-72 genes out of 22,600).
- Vimentin was consistently upregulated across all three mouse models (progressive motor neuronopathy, wobbler, SOD1(G93A)).
- Vimentin expression correlated with the severity of motoneurone degeneration.
Conclusions:
- Early molecular changes, including vimentin upregulation, are implicated in motoneurone degeneration.
- Disease pathogenesis likely involves complex, multipathway induction rather than a single pathway.
- This study provides the first comprehensive comparison of early gene de-regulation in three distinct motoneurone disease models.
