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Journal of Neuroscience, Vol 14, 6956-6966, Copyright © 1994 by Society for Neuroscience
Modulation of axon diameter and neurofilaments by hypomyelinating Schwann cells in transgenic mice
JS Cole, A Messing, JQ Trojanowski and VM Lee
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical School, Philadelphia 19104.
Studies of peripheral nerves in two different lines of hypomyelinating
transgenic mice support the hypothesis that myelinating Schwann cells exert
a significant influence on key biological properties of axons. The mice
contain transgenes combining the peripheral myelin protein zero gene (P0)
promoter and either the diphtheria toxin A chain gene product or the SV40
(simian virus 40) large T antigen. The consequences of peripheral nerve
hypomyelination on axon diameter, neurofilament (NF) density, and NF
phosphorylation were analyzed. The sciatic nerves of the P0 diphtheria
toxin A transgenic mice (DT) evidenced the most severe hypomyelination, and
this was associated with a dramatic decrease in NF phosphorylation plus a
marked increase in NF density. In contrast, the sciatic nerves in the P0
SV40 large T antigen transgenic mice (SV40) were not as severely
hypomyelinated and there was a milder decrease in NF phosphorylation plus a
more modest increase in NF density. Further, the sciatic nerves in both
lines evidenced a decrease in axonal caliber without any change in NF
content. Taken together, these studies provide strong evidence indicating
that myelinating Schwann cells exert a significant influence on axon
caliber by modulating NF phosphorylation and NF packing density in the
axons of peripheral nerves. Thus, key biological properties of axons are
modulated by signals transmitted from myelinating Schwann cells to axons of
peripheral nerves.
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