Sodium channel distribution in axons of hypomyelinated and MAG null mutant mice.
Na+ channel organization was studied with immunofluorescence in the peripheral nervous system of mice genetically altered to produce abnormal myelin. In two of these strains, transcription of inserted transgenes was targeted to myelinating Schwann cells through linkage to a promoter for the myelin protein P0. Adults of both of these strains had hindlimb paralysis and a tremor on lifting by the tail. In one case, Schwann cells were eliminated via expression of the diphtheria toxin A chain (DT-A). During postnatal days 3-7, Na+ channel clustering at forming nodes was dramatically reduced compared with that of normal animals. At 1-3 months of age, Na+ channel immunofluorescence was often found spread over long stretches of the axolemma, instead of being confined to nodal gaps. In the second P0-linked transgenic model, Schwann cell expression of the large T antigen tsA-1609 resulted in cell cycle dysfunction. Adult axons had regions of diffuse Na+ channel labeling. Focal clusters were rare within these zones, which were characterized by a series of cells of myelinating phenotype tightly apposed to the axon. Previous studies suggested that Schwann cells had to reach the stage of ensheathment characterized by periaxonal myelin associated glycoprotein (MAG) expression in order to induce Na+ channel clustering. However, in MAG-deficient mice, Na+ channel labeling patterns within sciatic nerves were normal.
Vabnick
I
I
Department of Biophysics, University of Rochester, New York 14642, USA.
Messing
A
A
Chiu
S Y
SY
Levinson
S R
SR
Schachner
M
M
Roder
J
J
Li
C
C
Novakovic
S
S
Shrager
P
P
D000375:Aging / Q000378:metabolism; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000502:physiology; D001369:Axons / Q000378:metabolism*; D004167:Diphtheria Toxin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic / Q000235:genetics; D009186:Myelin Sheath / Q000502:physiology*; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D015222:Sodium Channels / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
D000957:Antigens, Viral, Tumor; D004167:Diphtheria Toxin; D018992:Myelin-Associated Glycoprotein; D015222:Sodium Channels