SODIUM-CHANNEL DISTRIBUTION IN AXONS OF HYPOMYELINATED AND MAG NULL MUTANT MICE

Na+ channel organization was studied with immunofluorescence in the pe ripheral nervous system of mice genetically altered to produce abnorma l myelin. In two of these strains, transcription of inserted transgene s was targeted to myelinating Schwann cells through linkage to a promo ter for the myelin protein P-0. Adults of both of these strains had hi ndlimb paralysis and a tremor on lifting by the tail, In one case, Sch wann cells were eliminated via expression of the diphtheria toxin A ch ain (DT-A). During postnatal days 3-7, Na+ channel clustering at formi ng 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 P-0-linked transgenic model, Schwann cel l expression of the large T antigen tsA-1609 resulted in cell cycle dy sfunction. Adult axons had regions of diffuse Na+ channel labeling. Fo cal clusters were rare within these zones, which were characterized by a series of cells of myelinating phenotype tightly apposed to the axo n. Previous studies suggested that Schwann cells had to reach the stag e of ensheathment characterized by periaxonal myelin associated glycop rotein (MAG) expression in order to induce Na+ channel clustering, How ever, in MAG-deficient mice, Na+ channel labeling patterns within scia tic nerves were normal. (C) 1997 Wiley-Liss, Inc.