BIOCHEMICAL AND IMMUNOHISTOCHEMICAL STUDIES ON DYSMYELINATION OF QUAKING MUTANT MICE INVIVO AND INVITRO

Dysmyelination in the CNS of the quaking mutant mouse was studied biochemically and immunohistochemically. Measuring CNPase [cyclic nucleotide phosphohydrolase] activity showed that myelination in the CNS of quaking mice was affected to a different degree in different areas. The pallium cerebri was the most severely affected and the medulla and spinal cord were least affected. The density of astroglia observed by GFA [glial fibrillary acidic protein] staining was higher in the white matter of quaking mice than in controls, but the total area of the white matter in the cerebellum was smaller in the quaking mice than in the controls. The DNA content in the pallium cerebri and brain stem showed no increase and that of the cerebellum was even lower in quaking mice than in the controls. Hypertrophy of the astroglia was observed in the white matter of the cerebellum of quaking mice, though Bergmann astroglial fibers in the molecular layer did not show any hypertrophy. The cerebella of quaking mice in primary culture showed very poor myelination under the phase-contrast microscope. Purkinje cells from the quaking mutants appeared normal with regard to Bodian silver impregnation, hematoxylineosin staining, and Purkinje cell specific P400 protein. Addition of the conditioned culture medium of qk/qk to the culture of the control cerebellum did not interfere with the myelination. The cause of dysmyelination in the quaking mouse could be a genetic defect of the oligodendroglia rather than hypertrophy of the astroglial cells.