THE TAIEP RAT - A MYELIN MUTANT WITH AN ASSOCIATED OLIGODENDROCYTE MICROTUBULAR DEFECT

This report describes a new inherited disorder of myelination in the at, named taiep, in which failure of normal myelination of the CNS and subsequent demyelination result in a progressive neurological disturbance. At two months of age, myelin is present throughout the spinal cord, but is immature in the fasciculus gracilis and corticospinal tracts despite the presence of abundant oligodendrocytes. By 12 months, myelin has largely been lost in these spinal cord tracts and also in more rostral parts of the CNS, such as the cerebellum and optic nerves. Other funiculi of the spinal cord show a more diffuse lack of myelin. Oligodendrocytes develop a unique cellular abnormality, most obviously in older rats, which is characterized by the accumulation of microtubules throughout their cytoplasm. As the mutant rat's age, there is a continued protracted breakdown of myelin throughout the CNS, with evidence suggesting either persistent hypomyelination or attempts at remyelination of affected axons. It is proposed that the microtubular defect in oligodendrocytes results in a disruption of the normal myelination process in certain areas of the CNS of this mutant, and eventually leads to failure of maintenance of the myelin sheath.