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© The Rockefeller University Press, 0021-9525/1998//727 $5.00
The Journal of Cell Biology, Volume 141, Number 3, , 1998 727-739

Articles

Absence of the Mid-sized Neurofilament Subunit Decreases Axonal Calibers, Levels of Light Neurofilament (NF-L), and Neurofilament Content



Gregory A. Elder*, Victor L. Friedrich, Jr.{ddagger}, Paolo Bosco{ddagger}, Chulho Kang{ddagger}, Andrei Gourov*, Pang-Hsien Tu§, Virginia M.-Y. Lee§, and Robert A. Lazzarini{ddagger}

* Department of Psychiatry, and {ddagger} 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

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.

Abbreviations used in this paper: CNS, central nervous system; ES, embryonic stem; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IF, intermediate filament; Neo, neomycin; NF-H, heavy neurofilament; NF-L, light neurofilament; NF-M, mid-sized neurofilament; NF, neurofilament; PGK, phosphoglycerol kinase; PNS, peripheral nervous system.

Address all correspondence to Dr. Robert A. Lazzarini, Brookdale Center for Developmental and Molecular Biology, Box 1126, Mount Sinai School of Medicine, New York, NY 10029. Tel.: (212) 241-4272. Fax: (212) 860-9279. E-mail: rlazzar{at}smtplink.mssm.edu


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