Bartlett W P, Skoff R P
J Neurosci. 1986 Oct;6(10):2802-12. doi: 10.1523/JNEUROSCI.06-10-02802.1986.
The jimpy mutation results in severe hypomyelination throughout the CNS of hemizygous male mice. In the female carrier of the jimpy gene, partial hypomyelination is predicted as a consequence of genetic mosaicism resulting from random X-chromosome inactivation. The spinal cord of the female carrier was studied morphologically to determine if hypomyelination is present, the manner in which a possible myelin deficit is expressed, and the extent, if any, of compensation. The spinal cords of 14- to 15-d-old heterozygotes were found to be hypomyelinated. A deficit of 31% in the amount of myelin as compared to controls was detected in these young carriers by point-counting stereology. By the end of the first month the deficit was 12%, and after the fifth month complete recovery had occurred. These results demonstrate that the neuroglial cells are capable of compensating totally for the jimpy defect over a several month period. The reduction in the amount of myelin at 2 weeks postnatally is due to the ensheathment of fewer axons than normal and the formation of myelin sheaths that are thinner than normal. It is not due to a significant reduction in amount of axoplasm and a corresponding decrease in amount of myelin. This finding indicates that overall brain development is not retarded but that expression of the jimpy gene selectively affects the glial cells. Our morphologic studies also suggest that the neuron is not the target of the jimpy mutation. One line of evidence for this statement is that virtually all the axons are partially ensheathed, a condition that should not occur if 50% of the neurons are defective in the mosaic. The coexistence of both normal and defective cells within the same cell population and the apparent sparing of the neuron makes the female carrier of the jimpy gene an excellent model for studying mechanisms of compensation and plasticity of neuroglial cells.
jimpy突变导致半合子雄性小鼠整个中枢神经系统严重髓鞘形成不全。在jimpy基因的雌性携带者中，由于随机X染色体失活导致的遗传嵌合现象，预计会出现部分髓鞘形成不全。对雌性携带者的脊髓进行形态学研究，以确定是否存在髓鞘形成不全、可能的髓鞘缺陷的表现方式以及补偿的程度（如果有的话）。发现14至15日龄杂合子的脊髓髓鞘形成不全。通过点计数体视学在这些年轻携带者中检测到与对照组相比髓鞘量减少了31%。到第一个月末，缺陷率为12%，第五个月后完全恢复。这些结果表明，神经胶质细胞能够在几个月的时间内完全补偿jimpy缺陷。出生后2周时髓鞘量的减少是由于包裹的轴突比正常情况少，以及形成的髓鞘比正常情况薄。这不是由于轴浆量的显著减少和相应的髓鞘量减少。这一发现表明，整体脑发育没有延迟，但jimpy基因的表达选择性地影响神经胶质细胞。我们的形态学研究还表明，神经元不是jimpy突变的靶点。支持这一说法的一条证据是，几乎所有的轴突都有部分髓鞘包裹，如果嵌合体中50%的神经元有缺陷，这种情况是不会发生的。同一细胞群体中正常细胞和缺陷细胞的共存以及神经元明显未受影响，使得jimpy基因的雌性携带者成为研究神经胶质细胞补偿机制和可塑性的优秀模型。
