Differences in levels of neuroglial cell death in jimpy male mice and carrier females.

Jimpy (jp) is an X-linked disorder which results in a variety of glial cell abnormalities and the virtual absence of myelin in the central nervous system (CNS) of affected males. Female heterozygote carriers of the jp gene are mosaics. The wild-type genome will be expressed in roughly half of their cells, while in the other half the jp genome will be expressed. We have exploited this characteristic in order to determine whether the premature oligodendroglial death previously described in jp males is a primary effect of the mutation. Mosaic spinal cords were examined at the light-microscopic level for the presence of pyknotic cells at ages when oligodendroglial death is quite pronounced in jp males. The percentage of pyknotic glial cells (less than 0.6%) is not statistically different in normal and mosaic females at 5 and 30 days. At 14-15 days there is a slight increase in mosaic cords (1.2 vs. 0.75%) but there are still 10 times more dying glia in jp male cords of the same age. The low level of oligodendroglial death in mosaic spinal cords suggests that it is secondary to some other jp abnormality. Small increases in glial death over a protracted period of time could result in lower numbers of oligodendrocytes in older mosaics. Even if this occurs, the data still support the idea that the phenotype of genetically jp cells can be favorably altered by the mosaic environment.