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Mice with disrupted midsized and heavy neurofilament genes lack axonal neurofilaments but have unaltered numbers of axonal microtubules
Author(s) -
Elder Gregory A.,
Friedrich Victor L.,
Pereira Daniel,
Tu PangHsien,
Zhang Bin,
Lee Virginia M.Y.,
Lazzarini Robert A.
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990701)57:1<23::aid-jnr3>3.0.co;2-a
Subject(s) - neurofilament , microtubule , microbiology and biotechnology , neuroscience , axoplasmic transport , biology , immunology , immunohistochemistry
Mammalian neurofilaments are assembled from the light (NF‐L), midsized (NF‐M), and heavy (NF‐H) neurofilament proteins. While NF‐M and NF‐H cannot self‐assemble into homopolymers, the data concerning NF‐L has been more contradictory. In vitro bovine, porcine, and murine NF‐L can homopolymerize in the absence of other subunits. However, in vivo studies suggest that neither rat nor mouse NF‐L can form filaments when transfected alone into cells lacking endogenous intermediate filaments. By contrast, human NF‐L forms homopolymers in similar cell lines. Recently we generated mice with null mutations in the NF‐M and NF‐H genes. To determine if mouse NF‐L can homopolymerize in mouse axons, NF‐M and NF‐H null mutants were bred to create a line of double mutant animals. Here we show that axons in NF‐M/H double mutant animals are largely devoid of 10‐nm filaments. Instead, the axoplasm is transformed to a microtubule‐based cytoskeleton—although the lack of any increase in tubulin levels per unit length of nerve or of increases in microtubule numbers relative to myelin sheath thickness argues that microtubules are not increased in response to the loss of neurofilaments. Thus in vivo rodent neurofilaments are obligate heteropolymers requiring NF‐L plus either NF‐M or NF‐H to form a filamentous network. J. Neurosci. Res. 57:23–32, 1999. © 1999 Wiley‐Liss, Inc.