Hereditary hypertrophic neuropathy in the trembler mouse. Part 2. Histopathological studies: electron microscopy

The Trembler mouse suffers from a dominantly inherited hypertrophic neuropathy. Electron microscopy, including a quantitative analysis of myelination was performed on the nerves of Trembler mice from birth to senility and compared with the findings in control mice. Axons in adult Trembler nerves were thinly myelinated and were surrounded by very few myelin lamellae which in turn were often uncompact circumferentially and longitudinally. Schwann cell cytoplasm was copious and had a normal content of organelles. Well-developed "onion-bulb" formations which consisted of thinly myelinated axons surrounded by empty membrane configurations were frequently seen. The initiation of myelination was studied. The diameter distribution of promyelin fibres of control and Trembler sciatic nerve at ages day 2, j, and 7 was calculated Myelination in Trembler nerves commenced on axons of larger diameters than controls. The effectiveness of myelination was studied by relating the number of turns of myelin to the axon area of control and Trembler sciatic nerves from age 2 days to adult mice. At all ages Trembler axons were less well myelinated than controls and the difference was more pronounced with age. Schwann cell activity was examined by relating the area of the Schwann cell cytoplasm to the area of the axon it invests. The relative amount of Schwann cell cytoplasm decreased progressively in control axons with age and as the axon became better myelinated. By contrast, that of Tremblers did not undergo a similar reduction as the animal matured and the relative amount of Schwann cell cytoplasm was markedly increased in adult Tremblers when compared with controls. The periodicity of control and Trembler compact myelin was compared. The myelin period of Trembler mouse was significantly greater than that of controls. The defect in Trembler peripheral nerves was considered to be that of dysmyelinogenesis. The Schwann cell was active but ineffective in the synthesis, compaction and maintenance of myelin.