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Nerve conduction abnormalities in aging mice deficient for myelin‐associated glycoprotein
Author(s) -
Weiss Michael D.,
Luciano Carlos A.,
Quarles Richard H.
Publication year - 2001
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.1159
Subject(s) - myelin , myelin associated glycoprotein , nerve conduction velocity , electrophysiology , neurofilament , schwann cell , compound muscle action potential , biology , endocrinology , medicine , pathology , chemistry , neuroscience , microbiology and biotechnology , central nervous system , immunohistochemistry
Ultrastructural, biochemical, and electrophysiological analyses were done on 12–14‐month‐old mice deficient for myelin‐associated glycoprotein (MAG) to further characterize the neuropathy that develops as they age. Electron microscopy demonstrated normal myelin compaction and axonal degeneration in a large number of myelinated nerve fibers. Western blots showed that the proteins of compact myelin, P0 glycoprotein, and myelin basic protein were not significantly altered in the mutants; however, the Schwann cell protein, 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase, was reduced to less than half the control level. Also, both total and phosphorylated high‐molecular‐weight neurofilament proteins (TNFH and PNFH, respectively) were significantly decreased, as was the PNFH:TNFH ratio. Electrophysiological evaluation revealed a mild, but statistically significant, reduction of conduction velocity and a nonsignificant mild decrease in compound muscle action potential amplitudes. This constellation of findings in aging MAG‐null mice is consistent with an axonopathy that resembles axonal Charcot–Marie–Tooth (CMT2) disease in many respects. Thus, mutation of a myelin‐associated gene expressed by Schwann cells can induce axonal degeneration and cause a neuropathy with minimal signs of demyelination. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1380–1387, 2001