Development of onion bulb neuropathy in the Trembler mouse. Comparison with normal nerve maturation

The Trembler mouse is a neurological mutant showing dominant inheritance. Adult animals show a segmental demyelinating lesion of the peripheral nerves characterized by prominent onion bulb formation which is very similar to that of human hypertrophic interstitial neuropathy. Electron microscopic study of the development of this lesion in Trembler mice nerves from 1 to 21 days of age shows: 1. Axon differentiation towards a mature 1:1 axon/Schwann cell relationship is retarded, and the initiation of myelin formation is delayed. 2. Compact myelin formation is often incomplete, and when produced undergoes rapid degeneration. 3. Schwann cells become reactive to the presence of myelin debris, undergo hypertrophy and hyperplasia resulting in digestion of myelin debris and remyelination. These processes lead to early onion bulb formation. The presence of normal axons associated with reactive changes in Schwann cells suggest that the Schwann cell change is primary and not secondary to an axonal disorder.