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Journal of Neuroscience, Vol 10, 1855-1865, Copyright © 1990 by Society for Neuroscience
Altered slow axonal transport and regeneration in a myelin-deficient mutant mouse: the trembler as an in vivo model for Schwann cell-axon interactions
S de Waegh and ST Brady
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas 75235.
The thickness of the myelin sheath in normal myelinated nerve is
proportional to the diameter of the axon. In the demyelinating mutant
mouse, Trembler, not only is the thickness of the myelin sheath reduced,
but the caliber of associated axons is smaller. This correlation suggests
that the interaction between axons and Schwann cells may affect the shape
and function of axons as well as properties of myelin. Since axonal
diameter depends in part on the cytoskeleton and its movement with slow
axonal transport, we have compared the properties of slow transport in the
sciatic nerve of control and Trembler mice. Studies of the sciatic nerve of
normal mice showed that the rates for proteins moving in slow component a
(SCa) and slow component b (SCb) are similar to those previously measured
in rat. In Trembler mice, tubulin was transported significantly faster than
in control mice, with a rate of 1.73 mm/d for Trembler compared to 1.56
mm/d in the control. In contrast, the rate for neurofilament proteins was
significantly slower in the Trembler (1.15 mm/d compared to 1.38 mm/d in
the control). The majority of proteins in SCb were also transported slower
in Trembler than control: actin and calmodulin were transported at 2.29
mm/d as compared to 2.73 mm/d in control, while spectrin and clathrin were
transported at 2.01 and 2.43 mm/d, respectively, as compared to 2.54 mm/d
in control. The importance of slow axonal transport in regeneration has
been suggested by the clear correlation between the rates of regeneration
and the rates of SCb. Therefore, we evaluated regeneration of motor axons
in Trembler mice to determine whether the regenerative response was
affected by deficient Schwann cells. A slower regeneration rate was found
in the Trembler (1.7 mm/d) motor axon when compared to the control (2.29
mm/d), but elongation of fibers in regeneration began after a shorter delay
in the Trembler (1.6 d) than in control (2.5 d). Thus, deficient Schwann
cells and poor myelination appear to affect both quantitative and
qualitative properties of slow axonal transport. These changes lead to
alterations in the morphological and physiological properties of affected
axons.
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