Extra neurofilament NF-L subunits rescue motor neuron disease caused by overexpression of the human NF-H gene in mice.
J Neuropathol Exp Neurol
; 58(10): 1099-110, 1999 Oct.
Article
en En
| MEDLINE
| ID: mdl-10515233
ABSTRACT
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Expresión Génica
/
Terapia Recuperativa
/
Proteínas de Neurofilamentos
/
Enfermedad de la Neurona Motora
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Neuropathol Exp Neurol
Año:
1999
Tipo del documento:
Article
País de afiliación:
Canadá