THE TEMPORAL PROGRESSION OF THE MYELINATION DEFECT IN THE TAIEP RAT

The Sprague Dawley myelin mutant, the taiep rat, demonstrates a defect in CNS myelination which worsens with age and which is associated wit h abnormal accumulations of microtubules in oligodendrocytes. Quantita tive and qualitative electron microscopic studies of myelin developmen t and oligodendrocyte morphology were used to describe the temporal de velopment of the defect in this mutant, in three regions of the CNS. T he results indicate that the time of onset of myelination is similar i n mutant and control rats, however the amount of myelin formed is redu ced in the mutant, compared to controls, and there is a loss of myelin from the taiep CNS as the animals age. Thus the myelination defect in taiep has features of both hypomyelination and demyelination. Oligode ndrocyte microtubule abnormalities were noted in each region of the ta iep CNS at the time of onset of myelination. The earliest changes seen were close associations of oligodendrocyte microtubules with endoplas mic reticulum, with marked accumulations of microtubules filling the c ytoplasm of oligodendrocytes from older taiep rats. These findings sug gest that the microtubule abnormality in the taiep mutant inhibits bot h the initial formation and the long-term maintenance of myelin by the oligodendrocyte. in addition, there is also evidence to suggest that although the microtubule abnormality is present in oligodendrocytes th roughout the taiep CNS, it results in a more marked defect in the myel ination of axons of small diameter.