Expression of the jimpy gene in the spinal cords of heterozygous female mice. I. An early myelin deficit followed by compensation.
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.
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D003593:Cytoplasm / Q000648:ultrastructure; D005260:Female; D005786:Gene Expression Regulation; D006579:Heterozygote; D051379:Mice; D008816:Mice, Jimpy / Q000235:genetics*; D008818:Mice, Neurologic Mutants / Q000235:genetics*; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000648:ultrastructure; D013116:Spinal Cord / Q000502:physiology*