PMID:10461886

Citation	Jacomy, H, Zhu, Q, Couillard-Després, S, Beaulieu, JM and Julien, JP (1999) Disruption of type IV intermediate filament network in mice lacking the neurofilament medium and heavy subunits. J. Neurochem. 73:972-84
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.
Links	PubMed
Keywords	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
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