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J. Cell Biol.,
Volume 141, Number 3, May 4, 1998 727-739
* Department of Psychiatry, and Neurofilaments (NFs) are prominent components of large myelinated axons and probably the most
abundant of neuronal intermediate filament proteins.
Here we show that mice with a null mutation in the
mid-sized NF (NF-M) subunit have dramatically decreased levels of light NF (NF-L) and increased levels
of heavy NF (NF-H). The calibers of both large and
small diameter axons in the central and peripheral nervous systems are diminished. Axons of mutant animals
contain fewer neurofilaments and increased numbers of microtubules. Yet the mice lack any overt behavioral
phenotype or gross structural defects in the nervous
system. These studies suggest that the NF-M subunit is
a major regulator of the level of NF-L and that its presence is required to achieve maximal axonal diameter in
all size classes of myelinated axons.
Brookdale Center for Developmental and Molecular Biology, Mount Sinai School of Medicine,
New York 10029; and § Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine,
Philadelphia, Pennsylvania 19104
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