Selective myelin defects in the anterior medullary velum of the taiep mutant rat.
The taiep rat is a myelin mutant in which initial hypomyelination is followed by progressive demyelination of the CNS. An in vitro study suggests that accumulation of microtubules within oligodendrocytes is the cause of the taiep myelin defects (Song et al., 1999). In this article, we analyze microtubule accumulation in relation to taiep myelin defects in vivo in the anterior medullary velum (AMV), a CNS tissue that enables entire oligodendrocyte units to be resolved. Immunohistochemical analysis demonstrated notably high levels of beta-tubulin and the microtubule associated protein tau in the somata and processes of taiep oligodendrocytes. This was correlated with markedly reduced expression of the myelin proteins, proteolipid protein (PLP), myelin basic protein (MBP), 2',3 -cyclic nucleotide 3'-phosphodiesterase, and both large (L) and small (S) isoforms of myelin-associated glycoprotein (MAG). Moreover, PLP and L-MAG, which are dependent on the microtubule system for intracellular transport, accumulated in the perinuclear cytoplasm of the taiep oligodendrocyte. The myelin deficit was most marked in the area of the AMV populated by the small somata oligodendrocytes that have fine long processes that support numerous myelin sheaths of small diameter axons. Type III/IV oligodendrocytes, which have large somata and short processes that support a small number of myelin sheaths of large diameter axons, were also affected to a certain degree in compact myelin sheath formation. These results support the hypothesis that myelin loss and oligodendrocyte disruption in the taiep mutant result from a defect in the microtubule system that transports myelin components from the somata to the myelin sheath.
Song
J
J
Department of Medical Science, Shool of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA. songj@svm.vetmed.wisc.edu
Goetz
B D
BD
Kirvell
S L
SL
Butt
A M
AM
Duncan
I D
ID
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001933:Brain Stem / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020546:Fourth Ventricle / Q000473:pathology; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000378:metabolism* / Q000473:pathology; D008868:Microtubule Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism / Q000473:pathology; D009185:Myelin Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011922:Rats, Mutant Strains / Q000002:abnormalities / Q000378:metabolism; D017207:Rats, Sprague-Dawley
D008868:Microtubule Proteins; D009185:Myelin Proteins