Nerve conduction abnormalities in aging mice deficient for myelin-associated glycoprotein.
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.
Weiss
M D
MD
Myelin and Brain Development Section, NINDS, National Institutes of Health, Building 49, Room 2A28, Bethesda, Maryland 20892, USA.
Luciano
C A
CA
Quarles
R H
RH
D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D003711:Demyelinating Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004594:Electrophysiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000737:chemistry / Q000473:pathology; D018992:Myelin-Associated Glycoprotein / Q000032:analysis / Q000235:genetics*; D009431:Neural Conduction; D016900:Neurofilament Proteins / Q000032:analysis; D012583:Schwann Cells / Q000473:pathology; D012584:Sciatic Nerve / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure
D018992:Myelin-Associated Glycoprotein; D016900:Neurofilament Proteins; C051774:neurofilament protein H