The effect of the mouse mutation claw paw on myelination and nodal frequency in sciatic nerves.
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.
Department of Physiology and Biophysics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
A G
AG
Koszowski
G C
GC
Owens
S R
SR
Levinson
D000818:Animals; D001369:Axons / Q000502:physiology; D015415:Biomarkers; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009186:Myelin Sheath / Q000502:physiology*; D010641:Phenotype; D011901:Ranvier's Nodes / Q000502:physiology*; D012584:Sciatic Nerve / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015222:Sodium Channels / Q000032:analysis
D015415:Biomarkers; D015222:Sodium Channels