Abnormal cell relationships in Jimpy mice: electron microscopic and immunocytochemical findings
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The mutant mouse strain Jimpy is characterized by a deficiency of myelin formation throughout the C.N.S. The cause of this hypomyelination is unknown. Based on previous reports, astrocytes, axons and oligodendrocytes are all altered, but no single cell type can be unequivocally defined as the primary target. Jimpy and age-matched normal mice were investigated using thin sectioning, freeze-fracturing and immunocytochemistry. We examined optic nerves and cervical spinal cords of Jimpy to determine which cells were morphologically altered during the period which precedes the onset of myelination and which cellular alterations persisted during myelinogenesis.
Abnormalities of astrocytes and axons were frequently observed in Jimpy not only during myelination but also in early postnatal development before mature oligodendrocytes were present. The early astrocytic changes included hyperplasia and alterations of both cytoplasm and plasma membrane. An unusually complex network of astrocytic processes divided the axons into very small groups. During myelination, astrocytic processes were found insinuated between the axons and myelin sheath and/or within the myelin lamellae. Immunocytochemical investigations also revealed a complex network of glial fibrillary acidic protein-positive processes in contact with the majority of the axons. At stages prior to myelination axonal alterations were detected. Most of the axons were not in close contact with one another and individual axons had an undulating and irregular course. In areas where axon separation by astrocytic processes occurred, axonal diameters were more variable than the homogeneously sized axons of the normal mice. Our immunocytochemical results at stages during myelination showed not only many myelin basic protein-positive processes around axons in Jimpy but also clearly immunostained myelin sheaths. This indicates that the myelinating glia present not only produce myelin basic protein but can also incorporate it into the myelin spiral. The presented results suggest that the mouse mutant Jimpy could be a model for disturbed cell interactions in the C.N.S. Therefore, the hypomyelination may not be attributed to a defect of a single cell but rather to a deficiency in both macroglial types and, perhaps, the axon as well.
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- Abnormal cell relationships in Jimpy mice: electron microscopic and immunocytochemical findings
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