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Forschungsdatenbank PMU-SQQUID

Extra neurofilament NF-L subunits rescue motor neuron disease caused by overexpression of the human NF-H gene in mice.
Meier, J; Couillard-Després, S; Jacomy, H; Gravel, C; Julien, JP;
J Neuropathol Exp Neurol. 1999; 58(10): 1099-1110.
Originalarbeiten (Zeitschrift)


Couillard-Després Sébastien


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.

Useful keywords (using NLM MeSH Indexing)




Axonal Transport



Gene Expression*

Genetic Vectors



Mice, Inbred C57BL

Mice, Transgenic/genetics

Motor Neuron Disease/genetics*

Motor Neuron Disease/metabolism

Motor Neuron Disease/pathology

Motor Neuron Disease/therapy*

Neurofilament Proteins/genetics*

Neurofilament Proteins/metabolism

Neurofilament Proteins/therapeutic use*


Protein Isoforms/metabolism

Protein Isoforms/therapeutic use

Salvage Therapy*

Find related publications in this database (Keywords)

amyotrophic lateral sclerosis
motor neuron disease
transgenic mice