Extra neurofilament NF-L subunits rescue motor neuron disease caused by overexpression of the human NF-H gene in mice
| Autor: | Hélène Jacomy, Sebastien Couillard-Despres, Jurgen Meier, Claude Gravel, Jean-Pierre Julien |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Genetically modified mouse
Pathology medicine.medical_specialty Neurofilament Genetic enhancement Genetic Vectors Gene Expression Mice Transgenic Biology digestive system Axonal Transport Pathology and Forensic Medicine Adenoviridae Pathogenesis Cellular and Molecular Neuroscience Mice Neurofilament Proteins Gene expression medicine Animals Humans Protein Isoforms Amyotrophic lateral sclerosis Motor Neuron Disease Cytoskeleton Salvage Therapy General Medicine Motor neuron medicine.disease Axons Cell biology Mice Inbred C57BL medicine.anatomical_structure Phenotype Neurology embryonic structures Axoplasmic transport Neurology (clinical) Atrophy |
| Zdroj: | Journal of neuropathology and experimental neurology. 58(10) |
| ISSN: | 0022-3069 |
| Popis: | Previous studies demonstrated that transgenic mice overexpressing human neurofilament heavy (hNF-H) protein develop a progressive motor neuron disease characterized by the perikaryal accumulations of neurofilaments resembling those found in amyotrophic lateral sclerosis (ALS). To further investigate this neurofilament-induced pathology, we generated transgenic mice expressing, solely or concomitantly, the hNF-H and the human neurofilament light (hNF-L) proteins. We report here that the motor neuron disease caused by excess hNF-H proteins can be rescued by overexpression of hNF-L in a dosage-dependent fashion. In hNF-H transgenic mice, the additional hNF-L led to reduction of perikaryal swellings, relief of axonal transport defect and restoration of axonal radial growth. A gene delivery approach based on recombinant adenoviruses bearing the hNF-L gene also demonstrated the possibility to reduce perikaryal swellings after their formation in adult mice. The finding that extra NF-L can protect against NF-H-mediated pathogenesis is of potential importance for ALS, particularly for cases with NF-H abnormalities. |
| Databáze: | OpenAIRE |
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