Quaking mouse: vacuolar degeneration of spinal roots

Quaking is a neurologic mutant mouse with hypomyelination of CNS and PNS. In this mutant mouse of over 6 months of age, extensive vacuolation was found in the nerve fibers of the spinal roots, mostly in the ventral root. Normal axoplasmic constituents, such as mitochondria, neurotubules, and neurofilaments were, in general, well preserved. Many of these vacuoles appeared to be intra-axonal and only a few showed direct continuity with dilated periaxonal space. However, moderately electron-dense fluffy materials were often found in both the vacuoles and in the dilated periaxonal space, and rare mononuclear cells were found within the vacuoles, suggesting that these vacuoles were likely to be dilated periaxonal spaces. The vacuoles tended to be found more often in the myelinated nerve fibers than non-myelinated fibers. The changes in the periaxonal spaces observed in the old quaking mice were closely similar to those found in the myelinated cultures maintained on low calcium medium (Blank et al. 1974). Since calcium is highly concentrated in the node-paranodal regions and may be involved in the adhesion of Schwann cell loops to the axolemma (Ellisman et al. 1979), disturbed calcium and possibly other ionic concentrations due to structural abnormalities of node and paranodal regions in quaking mouse (Suzuki and Zagoren 1977) are speculated to be responsible for such morphological changes of spinal root in this mutant mouse.