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J. Cell Biol.,
Volume 143, Number 1, October 5, 1998 195-205
* Department of Psychiatry, Neurofilaments (NFs) are prominent components of large myelinated axons. Previous studies have
suggested that NF number as well as the phosphorylation state of the COOH-terminal tail of the heavy neurofilament (NF-H) subunit are major determinants of
axonal caliber. We created NF-H knockout mice to assess the contribution of NF-H to the development of
axon size as well as its effect on the amounts of low and
mid-sized NF subunits (NF-L and NF-M respectively).
Surprisingly, we found that NF-L levels were reduced
only slightly whereas NF-M and tubulin proteins were unchanged in NF-H-null mice. However, the calibers
of both large and small diameter myelinated axons
were diminished in NF-H-null mice despite the fact
that these mice showed only a slight decrease in NF
density and that filaments in the mutant were most frequently spaced at the same interfilament distance
found in control. Significantly, large diameter axons
failed to develop in both the central and peripheral nervous systems. These results demonstrate directly that
unlike losing the NF-L or NF-M subunits, loss of NF-H
has only a slight effect on NF number in axons. Yet NF-H
plays a major role in the development of large diameter
axons.
Brookdale Center for Developmental and Molecular Biology, Mount Sinai School of Medicine,
New York, New York 10029; and § Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory
Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
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