The Journal of Neuroscience, August 1, 1998, 18(15):5859-5868
The Effect of the Mouse Mutation Claw Paw on
Myelination and Nodal Frequency in Sciatic Nerves
Adam G.
Koszowski1,
Geoffrey C.
Owens2, 3, and
S. Rock
Levinson1, 3
Departments of 1 Physiology and Biophysics and
2 Biochemistry and Molecular Genetics and
3 Program in Neuroscience, University of Colorado Health
Sciences Center, Denver, Colorado 80262
Despite the biophysical and clinical importance of differentiating
nodal and internodal axolemma, very little is known about the process.
We chose to study myelination and node of Ranvier formation in the
hypomyelinating mouse mutant claw paw
(clp). The phenotype of clp is delayed
myelination in the peripheral nervous system. The specific defect is
unknown but is thought to arise from a breakdown in the complex
signaling mechanism between axon and Schwann cell. Myelination was
assessed in sciatic nerve cross sections from adult and postnatal day
14 (P14) heterozygous and homozygous clp mice.
Antibodies to P0, myelin-associated glycoprotein (MAG), and neural cell
adhesion molecule were used to assess the stage of myelination.
P14 homozygous clp mice showed an atypical staining
pattern of immature myelin, which resolved into a relatively normal
pattern by adulthood. Sodium channel clustering and node of Ranvier
frequency were studied in whole-mount sciatic nerves with sodium
channel and MAG antibodies. P14 homozygous clp nerves again showed an atypical, immature pattern with diffuse sodium channel
clusters suggesting nodal formation was delayed. In the adult,
homozygous clp sciatic nerves displayed dramatically
shortened internodal distances. The data from this study support the
hypotheses that node of Ranvier formation begins with the onset of
myelination and that the number and location of nodes of Ranvier in the
sciatic nerve are determined by myelinating Schwann cells.
Key words:
internodal length; claw paw; sciatic nerve; node of Ranvier; sodium channel; immunocytochemistry; MAG; NCAM; P0
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