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Changes in microtubule stability and density in myelin-deficient shiverer mouse CNS axonsAltered axon-Schwann cell interactions in PNS myelin-deficient Trembler mice result in changed axonal transport rates, neurofilament and microtubule-associated protein phosphorylation, neurofilament density, and microtubule stability. To determine whether PNS and CNS myelination have equivalent effects on axons, neurofilaments, and microtubules in CNS, myelin-deficient shiverer axons were examined. The genetic defect in shiverer is a deletion in the myelin basic protein (MBP) gene, an essential component of CNS myelin. As a result, shiverer mice have little or no compact CNS myelin. Slow axonal transport rates in shiverer CNS axons were significantly increased, in contrast to the slowing in demyelinated PNS nerves. Even more striking were substantial changes in the composition and properties of microtubules in shiverer CNS axons. The density of axonal microtubules is increased, reflecting increased expression of tubulin in shiverer, and the stability of microtubules is drastically reduced in shiverer axons. Shiverer transgenic mice with two copies of a wild-type myelin basic protein transgene have an intermediate level of compact myelin, making it possible to determine whether the actual level of compact myelin is an important regulator of axonal microtubules. Both increased microtubule density and reduced microtubule stability were still observed in transgenic mouse nerves, indicating that signals beyond synaptogenesis and the mere presence of compact myelin are required for normal regulation of the axonal microtubule cytoskeleton.
Document ID
20040112512
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Kirkpatrick, L. L.
(University of Texas Southwestern Medical Center Dallas, Texas 75235, United States)
Witt, A. S.
Payne, H. R.
Shine, H. D.
Brady, S. T.
Date Acquired
August 21, 2013
Publication Date
April 1, 2001
Publication Information
Publication: The Journal of neuroscience : the official journal of the Society for Neuroscience
Volume: 21
Issue: 7
ISSN: 0270-6474
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: AG12646
CONTRACT_GRANT: NS23868
CONTRACT_GRANT: NS23320
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Neuroscience

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