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Developmental Neuroscience 1992

Caprine beta-mannosidosis: regional differences in deficits of CNS myelin proteins.

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J A Benjamins
L Nedelkoska
K L Lovell

キーワード

概要

Caprine beta-mannosidosis is an autosomal recessive disorder characterized by marked deficiency of beta-mannosidase activity, accumulation of oligosaccharides, and pathologic changes involving prominent dysmyelination. The myelin deficits show marked regional variation, with spinal cord mildly affected and many brain regions severely affected by morphologic criteria. In this study, levels of myelin basic protein (MBP) and proteolipid protein (PLP) were measured by immunoblotting in samples prepared from spinal cord, brainstem and cerebral hemispheres of normal and affected goats at 2-4 days (newborns) and 2-4 weeks of age. In affected goats, total levels of MBP in spinal cord were normal, while PLP levels were 60-70% of normal at both ages. In contrast, PLP and MBP in brainstem and cerebral hemispheres were severely decreased at both ages, with levels of PLP 10-13% and MBP 25-29% of normal in newborns, and generally more reduced at 2-4 weeks. When myelin fractions were isolated on 0.32/0.85 M sucrose gradients, yields were about 38 and 25% of normal in spinal cord at the two ages, but less then 3% of normal in brainstem. Yields of myelin-like fraction were decreased as well, but to lesser extents than yields of myelin. Myelin from spinal cord had a normal composition with regard to PLP and MBP content, while the myelin fraction from brainstem was markedly deficient in both proteins. This suggests formation of myelin with a very abnormal composition in brainstem, or inclusion of large amounts of membranes other than myelin in this fraction. The more severe deficits in brainstem and cerebral hemispheres compared to spinal cord are consistent with morphologic observations.(ABSTRACT TRUNCATED AT 250 WORDS)

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