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Disruption of type IV intermediate filament network in mice lacking the neurofilament medium and heavy subunits.
Jacomy, H; Zhu, Q; Couillard-Després, S; Beaulieu, JM; Julien, JP;
J Neurochem. 1999; 73(3): 972-984.
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Couillard-Després Sébastien

Abstract

To clarify the role of the neurofilament (NF) medium (NF-M) and heavy (NF-H) subunits, we generated mice with targeted disruption of both NF-M and NF-H genes. The absence of the NF-M subunit resulted in a two- to threefold reduction in the caliber of large myelinated axons, whereas the lack of NF-H subunits had little effect on the radial growth of motor axons. In NF-M-/- mice, the velocity of axonal transport of NF light (NF-L) and NF-H proteins was increased by about two-fold, whereas the steady-state levels of assembled NF-L were reduced. Although the NF-M or NF-H subunits are each dispensable for the formation of intermediate filaments, the absence of both subunits in double NF-M; NF-H knockout mice led to a scarcity of intermediate filament structures in axons and to a marked approximately twofold increase in the number of microtubules. Protein analysis indicated that the levels of NF-L and alpha-internexin proteins were reduced dramatically throughout the nervous system. Immunohistochemistry of spinal cord from the NF-M-/-;NF-H-/- mice revealed enhanced NF-L staining in the perikaryon of motor neurons but a weak NF-L staining in axons. In addition, axonal transport studies carried out by the injection of [35S]methionine into spinal cord revealed after 30 days very low levels of newly synthesized NF-L proteins in the sciatic nerve of NF-M-/-;NF-H-/- mice. The combined results demonstrate a requirement of the high-molecular-weight subunits for the assembly of type IV intermediate filament proteins and for the efficient translocation of NF-L proteins into the axonal compartment.


Useful keywords (using NLM MeSH Indexing)

Animals

Axons/physiology

Carrier Proteins/biosynthesis

Carrier Proteins/genetics

Electrophoresis, Polyacrylamide Gel

Immunoblotting

Immunohistochemistry

Intermediate Filament Proteins/genetics

Intermediate Filament Proteins/physiology*

Mice

Mice, Knockout

Microscopy, Electron

Molecular Weight

Neurofilament Proteins/chemistry

Neurofilament Proteins/deficiency*

Neurofilament Proteins/genetics

Neurofilament Proteins/metabolism

RNA/analysis

RNA/genetics


Find related publications in this database (Keywords)

neurofilaments
knockout mice
axonal transport
axonal caliber
alpha-internexin