The consequences of dysmyelination are poorly understood and vary widely in severity. The 'shaking' mouse, a quaking allele, is a spontaneously occurring autosomal recessive mutation discovered at NYU characterized by severe CNS dysmyelination and demyelination, a conspicuous action tremor and seizures in ∼25% of animals, but with normal muscle strength and a normal lifespan. In this study we characterized this animal using electron microscopy, electrophysiology, and fluorescently labeled dextran tracers to determine what might underlie its behavior and longevity. We show many unmyelinated axons in the CNS and thinner myelin in both the CNS and PNS. Paranodes in the CNS show transverse bands to be present in nearly all paranodes to a lesser extent than in control animals but to a much greater extent than in other 'myelin mutants' (CST-/-, CGT-/-, Caspr-/-).

Immunofluorescence studies show elongated nodes in the 'shaking' mutant, but Na⁺ and K⁺ channels remain separated, distinguishing this mutant from others that lack transverse bands. Conduction velocity in the spinal cord, measured in vivo, is slowed fourfold in the shaking animal. Permeability of the paranodal junction was examined in vivo using dextran tracers injected into the sciatic nerve. Neither the rate of permeability nor the size of particles admitted to the junction was changed in the shaking animal. We conclude that the essential difference between the 'shaking' mutant and others more severely affected is the presence of transverse bands, which serve to maintain paranodal structure over time as well as the organization of the axolemmal domains and thus underlie the mildness of the neurological impairment and the normal longevity of this mutant.