Omlin F X, Anders J J
J Neurocytol. 1983 Oct;12(5):767-84. doi: 10.1007/BF01258150.
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.
突变小鼠品系Jimpy的特征是整个中枢神经系统髓鞘形成缺陷。这种髓鞘形成不足的原因尚不清楚。根据先前的报道，星形胶质细胞、轴突和少突胶质细胞均发生了改变，但没有一种单一的细胞类型可以明确地被定义为主要靶点。使用薄切片、冷冻断裂和免疫细胞化学方法对Jimpy小鼠和年龄匹配的正常小鼠进行了研究。我们检查了Jimpy小鼠的视神经和颈脊髓，以确定在髓鞘形成开始之前哪些细胞在形态上发生了改变，以及在髓鞘形成过程中哪些细胞改变持续存在。在Jimpy小鼠中，不仅在髓鞘形成期间，而且在成熟少突胶质细胞出现之前的出生后早期发育阶段，经常观察到星形胶质细胞和轴突的异常。早期星形胶质细胞的变化包括增生以及细胞质和质膜的改变。一个异常复杂的星形胶质细胞突起网络将轴突分成非常小的组。在髓鞘形成期间，发现星形胶质细胞突起夹在轴突和髓鞘之间和/或髓鞘板层内。免疫细胞化学研究还揭示了一个与大多数轴突接触的胶质纤维酸性蛋白阳性突起的复杂网络。在髓鞘形成之前的阶段检测到轴突改变。大多数轴突彼此没有紧密接触，单个轴突有起伏和不规则的走向。在星形胶质细胞突起导致轴突分离的区域，轴突直径比正常小鼠大小均匀的轴突更具变异性。我们在髓鞘形成阶段的免疫细胞化学结果显示，在Jimpy小鼠中，不仅轴突周围有许多髓鞘碱性蛋白阳性突起，而且髓鞘也有明显的免疫染色。这表明存在的髓鞘形成胶质细胞不仅产生髓鞘碱性蛋白，而且还能将其整合到髓鞘螺旋中。所呈现的结果表明，小鼠突变体Jimpy可能是中枢神经系统中细胞相互作用紊乱的模型。因此，髓鞘形成不足可能不是归因于单个细胞的缺陷，而是归因于两种大胶质细胞类型的缺陷，也许还有轴突的缺陷。
