The taiep rat: A myelin mutant with an associated oligodendrocyte microtubular defect

Abstract

This report describes a new inherited disorder of myelination in the rat, 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 rats 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.

Progressive Deterioration of Central Components of Auditory Brainstem Responses during Postnatal Development of the Myelin Mutant <i>taiep</i> Rat

“…The myelin disorder that characterizes this mutant is probably due to a defect in oligodendrocytes [Duncan et al, 1992;Lunn et al, 1995;Couve et al, 1997], leading to a disruption in the development and maintenance of central, but not peripheral, myelin. Cross-breeding experiments indicate that taiep rats are affected by an autosomal recessive mutation [Holmgren et al, 1989].…”

“…The taiep rat is a neurological mutant [Holmgren et al, 1989;Prieto et al, 1991] characterized by abnormal myelination and subsequent demyelination of the CNS [Duncan et al, 1992;Lunn et al, 1997]. The myelin disorder that characterizes this mutant is probably due to a defect in oligodendrocytes [Duncan et al, 1992;Lunn et al, 1995;Couve et al, 1997], leading to a disruption in the development and maintenance of central, but not peripheral, myelin.…”

The Myelin Mutants as Models to Study Myelin Repair in the Leukodystrophies

“…The taiep is an autosomal recessive mutant found on a Sprague Dawley background [59]. It is a unique myelin mutant that initially demonstrates hypomyelination, and then severe demyelination of white matter in the brain, optic nerves, and the fasciculus gracilis and corticospinal tract of the dorsal column of the spinal cord [59].…”

“…It is a unique myelin mutant that initially demonstrates hypomyelination, and then severe demyelination of white matter in the brain, optic nerves, and the fasciculus gracilis and corticospinal tract of the dorsal column of the spinal cord [59]. The early failure of normal myelination and subsequent demyelination result from the progressive accumulation of microtubules in OLs [59,60].…”

“…It is a unique myelin mutant that initially demonstrates hypomyelination, and then severe demyelination of white matter in the brain, optic nerves, and the fasciculus gracilis and corticospinal tract of the dorsal column of the spinal cord [59]. The early failure of normal myelination and subsequent demyelination result from the progressive accumulation of microtubules in OLs [59,60]. This results in a disturbance in the polarity of microtubules and a disruption in the transport of molecules and mRNAs that utilize the microtubular network within the cytoplasm of OLs [61][62][63].…”