Nerve conduction abnormalities in aging mice deficient for myelin-associated glycoprotein

Ultrastructural, biochemical, and electrophysiological analyses were done o n 12-14-month-old mice deficient for myelin-associated glycoprotein (MAG) t o further characterize the neuropathy that develops as they age. Electron m icroscopy demonstrated normal myelin compaction and axonal degeneration in a large number of myelinated nerve fibers. Western blots showed that the pr oteins of compact myelin, PO glycoprotein, and myelin basic protein were no t significantly altered in the mutants; however, the Schwann cell protein, 2 ' ,3 ' -cyclic nucleotide 3 ' -phosphodiesterase, was reduced to less tha n half the control level. Also, both total and phosphorylated high-molecula r-weight neurofilament proteins (TNFH and PNFH, respectively) were signific antly decreased, as was the PNFH:TNFH ratio. Electrophysiological evaluatio n revealed a mild, but statistically significant, reduction of conduction v elocity and a nonsignificant mild decrease in compound muscle action potent ial amplitudes. This constellation of findings in aging MAG-null mice is co nsistent with an axonopathy that resembles axonal Charcot-Marie-Tooth (CMT2 ) disease in many respects. Thus, mutation of a myelin-associated gene expr essed by Schwann cells can induce axonal degeneration and cause a neuropath y with minimal signs of demyelination. (C) 2001 John Wiley & Sons, Inc.